IMPORTANCE There remains little experimental evidence and no randomized clinical trial to date to confirm the benefit of platelet-rich plasma (PRP) for facial rejuvenation. OBJECTIVE To investigate whether PRP injection improves the visual appearance, including texture and color, of photodamaged facial skin. DESIGN, SETTING, AND PARTICIPANTS In this randomized clinical trial, participants and raters were masked to groupings. The setting was an academic-based, urban outpatient dermatology practice in Chicago, Illinois. Participants were adults aged 18 to 70 years with bilateral cheek rhytids of Glogau class II or greater. The duration of the study was August 21, 2012, to February 16, 2016. INTERVENTIONS Each participant received 3 mL intradermal injections of PRP to one cheek and sterile normal saline to the contralateral cheek. MAIN OUTCOMES AND MEASURES Primary outcomes were photoaging scores (with subscores for fine lines, mottled pigmentation, roughness, and sallowness) as rated by 2 masked dermatologists. Secondary outcomes included participant self-assessment scores of improvement on a 5-point scale (worsening, no change, mild improvement, moderate improvement, or significant improvement), participant overall satisfaction scores on a 4-point scale (not satisfied, slightly satisfied, moderately satisfied, or very satisfied), and participant-reported or investigator-observed adverse events. RESULTS Of 27 enrolled participants, 19 (mean [SD] age, 46.37 [10.88] years; 17 female) were analyzed. Reported adverse events, which were not associated with the study agent, included redness (n = 18), swelling (n = 16), bruising (n = 14), pruritus (n = 1), skin scaling (n = 1), and dryness of skin (n = 1). No participants reported any adverse events at 12 months. Mean (SD) photoaging scores rated by 2 dermatologists showed no significant difference between PRP and normal saline for fine lines (baseline, 1.