BACKGROUND Perioral rhytides are a common complaint among dermatologic patients and can be notoriously stubborn and resistant to therapy. OBJECTIVE We aimed to assess the safety of fractional ablative laser-assisted delivery of topical poly-l-lactic acid (PLLA) suspension in the treatment of upper cutaneous lip rhytides. MATERIALS AND METHODS Prospective, single-arm, rater-blinded trial. Ten subjects with moderate to severe upper lip rhytides underwent 3 bimonthly treatments of low-density fractional carbon dioxide laser followed by topical application of PLLA suspension. Wrinkle severity before and after treatment was analyzed using computer-generated analyses. Blinded raters and subjects assessed improvement of wrinkles after treatment using the Global Aesthetic Improvement Scale (GAIS) (scores ranging from −3 to 3). Adverse events were recorded at each visit. RESULTS Treatments were well tolerated. Other than expected post–laser erythema, no unanticipated adverse events were noted. After 3 treatments, the severity of upper lip wrinkles decreased by an average of 47% (p < .05) as calculated by computer-generated image analyses. Blinded raters and subjects rated wrinkles as much improved after 3 treatments (score of 2 on the GAIS). CONCLUSION Laser-assisted delivery of PLLA is a safe and possibly effective treatment for upper lip rhytides.