Restylane Kysse: What the FDA Trial Found, Including the 30-Day Recovery Diary
Reviewed for medical accuracy against our Medical Review Board · Last updated 2 September 2026
Part of Dermal Fillers
Restylane Kysse is one of two products in the Restylane range approved for lips, and the newer of the two. The FDA approved it on 26 March 2020 for injection into the lips for lip augmentation and correction of upper perioral rhytids, the fine lines above the mouth, in adults over 21.
Its trial document is unusually useful, because subjects kept a 30-day diary. That diary contains the most honest account of lip filler recovery we have found anywhere, and it does not match how the procedure is usually sold.
The two numbers that matter most. 97.8% of patients reported an injection site reaction after their first treatment, and 29.1% rated it as affecting their daily activities. And the result fades on a measurable curve: 88% of patients were responders at 8 weeks, 60% at 48 weeks.
What Kysse is actually approved for
The approval wording is narrow and worth reading closely: injection into the lips for lip augmentation and correction of upper perioral rhytids, in patients over the age of 21. It came through P140029/S021, a supplement to the same FDA application that carries Refyne, Defyne and Contour.
Two things follow. First, the approval covers the lip body and the lines directly above the upper lip. It does not name the chin, the marionette lines or the jaw. Second, "over 21" is a real limit, not a formality: nobody under 21 was studied.
Kysse is a hyaluronic acid gel, so unlike Radiesse it can be dissolved with hyaluronidase if you dislike the result. For a first lip treatment that is worth more than most people realise. The full range and how the products divide up is on our Restylane hub.
What the trial asked, and what it did not
273 subjects were randomised 2 to 1, 184 to Kysse and 89 to a control. The control, in the FDA document's own words, was "a legally marketed product in the US with a similar indication for use". In other words, another approved lip filler.
That makes this a non-inferiority study. The question it set out to answer was whether Kysse falls short of an existing filler by more than an agreed margin. It passed. But the question it never asked was whether Kysse beats doing nothing at all to your lips.
That distinction matters more here than it sounds. On our chin filler and jawline pages, trials that did use untreated control groups produced an awkward finding: a meaningful share of people who received nothing were still scored as improved by a blinded evaluator. No such number exists for Kysse, because no one in this trial went untreated.
The primary measure was the Medicis Lip Fullness Scale, a 5-point scale running from "very thin" to "very full", assessed by a blinded evaluator, with the upper and lower lip scored separately as co-primary endpoints at 8 weeks after the last injection.
How well it worked, and for how long
Here is the full curve, which we have not seen published anywhere else. A responder is a patient whose lips improved by at least one grade on that 5-point scale, upper and lower combined.
| Weeks after last injection | Responders | 95% confidence interval |
|---|---|---|
| Week 8 | 88% (155/177) | 0.82 to 0.92 |
| Week 16 | 82% (142/174) | 0.75 to 0.87 |
| Week 24 | 77% (129/168) | 0.70 to 0.83 |
| Week 32 | 69% (115/167) | 0.61 to 0.76 |
| Week 40 | 66% (110/166) | 0.59 to 0.73 |
| Week 48 | 60% (101/169) | 0.52 to 0.67 |
Read the last row before booking. At 48 weeks, 60% of patients were still responders, which means 40% were not. "Kysse lasts up to a year" is defensible, but only if you accept that roughly two in five people no longer have a measurable result by then. The decline is gradual rather than sudden, and most of it happens between weeks 24 and 32.
The trial also measured the fine lines above the lip separately, using a Wrinkle Assessment Scale, and asked both the patient and a blinded evaluator for a global impression of improvement. For how this compares with other lip products, see how long lip filler lasts.
The 30-day diary, and why "minimal downtime" is wrong
This is the part of the document nobody quotes. Subjects recorded pre-defined events every day for 30 days after treatment, rating each as none, tolerable, affecting daily activities, or disabling. Following the initial treatment:
| Reaction | Patients reporting it |
|---|---|
| Any injection site reaction | 97.8% (179/183) |
| Swelling | 90.2% (165/183) |
| Tenderness | 87.4% (160/183) |
| Bruising | 85.8% (157/183) |
| Lumps or bumps | 84.2% (154/183) |
| Redness | 73.2% (134/183) |
| Pain | 68.3% (125/183) |
| Skin discoloration | 65.0% (119/183) |
| Itching | 35.0% (64/183) |
Nearly everyone had something. More than four in five had swelling, tenderness, bruising and lumps. Then the intensity, which is the number that should change how you plan:
- Tolerable: 67.6% (121 of 179)
- Affects daily activities: 29.1% (52 of 179)
- Disabling: 3.4% (6 of 179)
Nearly one in three patients said their recovery interfered with their daily life. That is the manufacturer's own trial, not a complaints database. Most reactions lasted two weeks or less, and the FDA labelling notes that lumps and bumps may last longer but usually resolve within 30 days.
So the practical planning advice is not "there is no downtime". It is: assume visible swelling and bruising, assume you can feel lumps for a couple of weeks, and do not book this in the fortnight before an event you care about. Our filler recovery guide covers what the first two weeks look like across products, and filler complications covers the rare things that are not part of normal recovery and need a phone call.
Kysse or Restylane Silk
Both are approved for lips within the same range, so the question comes up at consultation.
| Restylane Kysse | Restylane Silk | |
|---|---|---|
| Approved | 26 March 2020 | 13 June 2014 |
| FDA application | P140029/S021 | P040024/S072 |
| Approved for | Lip augmentation and upper perioral rhytids | Submucosal implantation for lip augmentation, and dermal implantation for perioral rhytids |
No trial has compared them, so no published evidence says one is better. The honest difference is that Kysse is the newer product with the more recent trial, and Silk's approval wording separates the two jobs by injection depth: submucosal for volume, dermal for the lines.
If you want lip movement rather than lip volume, neither is the answer. That is a Botox lip flip, which uses a neurotoxin and a few units rather than a filler, and does something quite different.
Who was actually in the trial
The study population was narrow, and worth knowing if you do not resemble it. The mean age was 52.8, 96.7% were female and 94.0% were White.
Lip filler is marketed heavily to people in their twenties, and this was a trial with a mean age in the fifties, where lip volume loss is usually age-related rather than a wish for a different lip shape. The results above come from that population. They are not evidence about a 24-year-old asking for a fuller shape, which is a legal and common treatment but not the one that was studied.
The near-total absence of men and the very low representation of darker skin types are the same pattern we found across the filler approvals. It is a limitation of the evidence base rather than of this product specifically.
What to ask before you book
- Kysse or Silk, and why? Both are approved for lips. No trial compares them, so the answer should be about your lips rather than about the brand.
- How much product, in total? Ask for the total volume across the initial treatment and any touch-up, not a single syringe price.
- What does the fortnight after actually look like? If the answer is "minimal downtime", show them the diary numbers. 97.8% had a reaction and 29.1% said it affected daily activities.
- When is my event? Do not book within two weeks of anything that matters.
- What happens if I hate it? Kysse is hyaluronic acid, so hyaluronidase dissolves it. Ask what that costs and who pays.
- What is the plan at nine months? 40% of patients were no longer responders by week 48, so a maintenance conversation is a real one, not a sales tactic.
For the rest of the range and how the eight products divide up by area, see our Restylane hub, and dermal fillers for what the FDA record shows across every approved filler.
Frequently asked questions
What is Restylane Kysse approved for?
How long does Restylane Kysse last?
What is recovery from Restylane Kysse really like?
Is Kysse better than Restylane Silk?
Can Restylane Kysse be dissolved?
What did the Kysse trial compare it against?
Am I too young for Restylane Kysse?
Sources
Every figure on this page was read from the documents below rather than from a clinic or a manufacturer's marketing. They open in a new tab so you can check any claim here against its source.
- Summary of Safety and Effectiveness Data, P140029/S021, Restylane Kysse, US Food and Drug Administration
- Dermal fillers (soft tissue fillers), US Food and Drug Administration
- Dermal fillers, American Society of Plastic Surgeons
Know the count before the quote. The unit count is half the bill, and a low per-unit rate recovered by a high unit count is the commonest way a deal is not one. How to tell.
Deciding which area, not how many units? Botox by facial area covers what each zone actually achieves, which four are FDA approved, and the things Botox cannot fix at all.
