This study aims to evaluate the clinical outcomes of arthroscopic autologous matrix-induced chondrogenesis (A-AMIC) for osteochondral lesions of the talus (OLT) at 24 months and 60 months of follow-up. The secondary aim was to assess whether age, body mass index (BMI), and lesion surface affect outcomes. Sixty-three patients (32 males, 31 females) with a median age of 37 years [interquartile range (IQR): 25-48] were included. Preoperative and postoperative (24 months and 60 months) clinical outcomes were evaluated using a Visual Analog Score (VAS) for pain during walking, the American Orthopaedic Foot and Ankle Society (AOFAS), Short-Form Survey (SF-12), the Halasi, and the University of California, Los Angeles (UCLA) scores. Patients were categorized according to age, BMI, and lesion surface (1-1.5 cm2 and over 1.5 cm2). The effect of each category was evaluated. There were significant improvements in the VAS, AOFAS, SF-12, and UCLA, comparing the preoperative scores to the 60-month follow-up scores (P < 0.001). There were no significant differences in the above-mentioned outcomes between the follow-up periods. Patients older than 33 years had lower SF-12, Halasi, and UCLA scores (P = 0.005, 0.004, and <0.001, respectively). Overweight patients had lower VAS, SF-12, Halasi, and UCLA scores (P = 0.006, 0.002, 0.024, and 0.007, respectively). Lesion size was uninfluential. A-AMIC yielded clinical improvements at a minimum follow-up of 60 months in patients with symptomatic OLTs, with clinical improvement peaking in the first 2 years, followed by a plateau period. Increased age and BMI were significantly associated with inferior outcomes.