BACKGROUND: ATX-101 (deoxycholic acid) causes adipocytolysis when injected into subcutaneous fat. OBJECTIVE: Evaluate the long-term safety and efficacy of ATX-101 for submental fat (SMF) reduction. METHODS: Adults (N=165) with moderate-to-extreme SMF received ≤6 treatments of open-label ATX-101 (2 mg/cm2) and were evaluated up to 12 months after last treatment. Efficacy end points included improvements in SMF based on clinician or subject assessment, patient-reported outcomes, downtime (via subject questionnaire), and skin laxity. Safety was evaluated throughout the study. RESULTS: Twelve weeks after last treatment, most subjects achieved a ≥1-grade improvement in SMF based on clinician (86.8%) or subject (83.8%) evaluation; at 12 months, 90.4% and 80.7% of these responders, respectively, maintained the response. Overall, 84.9% of subjects were satisfied with the appearance of their face/chin. At 12 months, 82.9% of subjects had unchanged, and 10.1% had improved, skin laxity relative to 12 weeks after last treatment. Adverse events were mild to moderate and mainly involved the treatment area. During the 7 days after the first treatment, 13.3% of subjects missed work and 33.9% missed social/leisure activities. Following subsequent treatments, 2.4%–6.0% of subjects missed work and 10.0%–15.7% missed social/leisure activities. CONCLUSION: The safety and efficacy of ATX-101 were sustained over 12 months. ClinicalTrials.gov identifier, NCT01426373 J Drugs Dermatol. 2019;18(9):870-877.