BACKGROUND: Adipose extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) contains adipose-derived stem cells, extracellular matrix, and other cell components, and possesses the ability to promote collagen production and serve as a filling agent. AIM: To assess the efficacy and safety of ECM/SVF-gel injection for the treatment of acne scars, compared to CO METHODS: We performed an open-label, investigator-initiated, assessor-blinded, split-face trial in Xijing Hospital, China, between July 11, 2020, and December 30, 2022. Patients exhibiting moderate to severe acne scars were randomly assigned to a single ECM/SVF-gel injection on one half of the face or two sessions of CO RESULTS: A total of 11 participants were enrolled, and 10 completed the follow-up. The mean age of patients was 27.5 ± 4.2, 7 female and four male, seven with Fitzpatrick skin Type III and four with Type IV. At 24weeks, the mean change in ECCA score was -60.25 on the side of ECM/SVF-gel injection and - 43.25 on the side of CO CONCLUSIONS: ECM/SVF-gel injection is an effective and safe approach in the treatment of acne scars. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT06116162.