Talar OsteoPeriostic grafting from the Iliac Crest (TOPIC) for large osteochondral lesions of the medial talar dome was shown to be effective at 2 years of follow-up. In this prospective cohort study, our aim was to evaluate the clinical and radiographic outcomes at 5 years of follow-up. The primary outcome was the Numeric Rating Scale (NRS) score for pain during walking. Secondary outcomes included NRS scores for pain during rest and during stair-climbing as well as scores on the Foot and Ankle Outcome Score (FAOS) subscales, Short Form (SF)-36 Physical Component Summary and Mental Component Summary scores, and the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score. Computed tomography (CT) scans were evaluated. Thirty-seven patients were included. Two patients died and 2 underwent ankle arthrodesis before 5 years and thus were not included in the 5-year statistical analysis of outcomes. The median NRS score for pain during walking improved from 7 (interquartile range [IQR], 5 to 8) preoperatively to 2 (IQR, 1 to 4) at 5 years (p < 0.001), surpassing the minimal clinically important difference. All secondary clinical outcomes improved significantly. All grafts showed incorporation, and 87% of the patients with a CT scan at 5 years demonstrated evidence of cyst formation. Osteoperiosteal autografting using the TOPIC technique is an effective treatment option for large medial osteochondral lesions of the talus, with durable results at 5 years of follow-up. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.