Osteochondral lesions of the talus (OLTs) are a common cause of post-traumatic ankle pain and disability. Atelocollagen-induced chondrogenesis (ACIC) aims to encourage the development of hyaline cartilage, which is biomechanically superior to fibrocartilage. This single-center, retrospective database study assessed patients who underwent arthroscopic microfracture with or without atelocollagen scaffold augmentation for OLT. Between 2010 and 2019, 87 patients underwent microfracture only and 31 patients underwent ACIC. Propensity score matching was used to match the ACIC group in a 1:2 ratio to a corresponding microfracture-only group using logistic regression. American Orthopaedic Foot & Ankle Society (AOFAS) scores, 100-mm Visual Analog Scale (VAS), Short Form-36 (SF-36), and satisfaction were assessed at preoperative, 3-, 6-, and 12-month intervals. There were no differences in baseline characteristics between groups after matching (P > .05). Both groups had similar improvements to VAS, AOFAS, and SF-36 scores up to 12 months (P > .05). Both groups had significant 1-year improvements to physical functioning, physical limitations in usual role activities, pain, and social functioning domains, but the ACIC group additionally had significant improvements to general health, vitality, and mental health. Patients in the ACIC group were also more satisfied than the microfracture group at all time points. Patients with OLTs who underwent ACIC reported superior satisfaction and improvements to quality of life, although clinical outcomes were similar to those who underwent microfracture alone at 1 year.Level of Evidence: Level III: Cohort study.