Purpose: To evaluate the safety and efficacy of onabotulinumtoxinA compared with placebo to reduce the appearance of platysma prominence in adult participants. Methods: This randomized, placebo-controlled, double-blind study evaluated onabotulinumtoxinA in participants with at least moderate platysma prominence (eg, vertical neck bands). Participants meeting all eligibility criteria were randomized in a 1:1:1 ratio to receive a single treatment of onabotulinumtoxinA high dose (HD), onabotulinumtoxinA low dose (LD), or placebo on day 1 and followed for 4 months. Efficacy was assessed by the investigator and participant independently using a valid severity scale, and analyzed by a serial gatekeeping multiple comparisons procedure. Results: A total of 171 participants enrolled; 169 were included in the safety population. Participants were predominantly female and white (each >92%); mean age was 50 years and mean body mass index was 22.9 kg/m2. Treatment with onabotulinumtoxinA HD and LD was associated with a significant ≥1-grade improvement versus placebo at day 14 by investigators (88.2%, 77.8% vs 12.0%, respectively; p<0.0001) and participants (88.2%, 75.9% vs 18.0%, respectively; p<0.0001). Most treatment-related adverse events (AEs) were procedure related, mild in severity, and consistent with previously published studies; all resolved by study end (HD, 18.5%; LD, 13.6%; placebo, 12.5%). There were no treatment-related serious adverse events. The most common onabotulinumtoxinA-related AE was neck muscle weakness, reported in 5 participants in the HD group. Conclusion: Treatment of platysma prominence with onabotulinumtoxinA HD or LD is more effective than placebo. OnabotulinumtoxinA yielded a safety profile consistent with the literature.