BACKGROUND: Cellulite is an aesthetic condition affecting the appearance of skin in certain body regions and is associated with body dissatisfaction, psychosocial stress, and decreased quality of life. Previous studies have established the safety and feasibility of a novel, minimally-invasive device utilized for precisely identifying and verifiably releasing septa responsible for cellulite depressions. The single procedure is known as Targeted Verifiable Subcision (TVS). OBJECTIVES: The objective of this single-arm, open-label, multicenter study was to evaluate the safety and efficacy of TVS for reducing the appearance of moderate to severe cellulite in the buttock and thighs of adult women. METHODS: Adult women 21-55 years of age and a BMI <30 kg/m2 with moderate or severe cellulite on the buttocks and/or thighs were eligible to be enrolled at 9 sites. Endpoint data includes results from 4 of the postprocedural follow-up visits at 24 hours, 7 days, 30 days, and 90 days (3 months). The primary endpoints were a mean ≥ 1 point reduction in the Cellulite Severity Scale (CSS) at 90 days and no related serious adverse events (SAEs) at 30 days. RESULTS: Seventy-four female participants with a mean BMI of 24.8 ± 2.7 and age of 41.4 ± 7.4 years received this single procedure. The mean improvement in CSS (N=68) was 1.5 ± 0.9 (p < 0.0001). There were no device-related SAEs at 30 days. CONCLUSIONS: Targeted Verifiable Subcision for selectively identifying and verifiably releasing septa responsible for cellulite depressions is an effective and safe means for improving the appearance of moderate to severe cellulite in adult women.