PurposeTo investigate the clinical efficacy and prognostic factors associated with autologous osteoperiosteal transplantation for the treatment of single cystic osteochondral lesions of the talus (OLT).MethodsThe clinical data of patients with single cystic OLT undergoing autologous osteoperiosteal transplantation at the Department of Foot and Ankle Surgery of our hospital between 2018 and 2022, including complete follow‐up, were retrospectively analyzed. Imaging data from each patient were imported into Mimics software to measure the surface area, volume and depth of the lesions. Then, the talus nine‐compartment partitioning method was used to partition the injury site. Preoperative and final follow‐up assessments were performed using the American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) for pain and 36‐item Short‐Form Health Survey (SF‐36) to evaluate treatment efficacy and analyze prognostic factors.ResultsOf the 31 patients with single cystic OLT with a complete set of follow‐up data, there were 17 males and 14 females, with a mean age of 43.3 ± 13.6 years, a mean follow‐up time of 30.1 ± 14.0 months and a mean illness duration of 30.4 ± 20.0 months. The postoperative final follow‐up AOFAS score was 90.7 ± 5.5; this represented significant improvement when compared to the preoperative score of 57.0 ± 8.5 (P < 0.001). The final postoperative follow‐up VAS score was 18.5 ± 8.3; this was significantly better than the preoperative score of 57.8 ± 8.7 (P < 0.001). The physical component summary (PCS) score and mental component summary (MCS) score on the SF‐36 scale showed significant improvement at the final postoperative follow‐up when compared to preoperative scores (p < 0.001). No other complications were observed during follow‐up, such as wound infection or pain at the donor site. One of the patients showed less improvement, which may be related to premature weight‐bearing or re‐sprained ankle after surgery. There was no significant correlation between the duration of illness, gender and the location, depth, surface area and volume of the OLT and the postoperative scores. However, patient age showed a significant negative correlation with the postoperative SF‐36 PCS and MCS scores.ConclusionAutologous osteoperiosteal transplantation for single cystic OLT demonstrated good clinical efficacy with a low incidence of complications. Furthermore, age represents an important factor influencing prognosis.Level of EvidenceLevel II.