Background <p>Post-traumatic osteoarthritis (PTOA) is a common and clinically important complication after ankle fracture surgery, but reliable individualized risk stratification remains limited. This study aimed to develop and externally validate a Cox-based risk prediction model for postoperative PTOA after ankle fracture surgery and to assess its incremental value over traditional early postoperative clinical evaluation indicators.</p> Methods <p>This prospective two-center cohort study consecutively enrolled patients with surgically treated ankle fractures from Center I (March 2020 to March 2024) and Center II (March 2021 to March 2024). After screening 964 patients, 812 were included, with 605 assigned to the training cohort and 207 to the external validation cohort. Structural PTOA, the primary endpoint, was defined as the first occurrence of Kellgren–Lawrence grade ≥ 2 on postoperative weight-bearing ankle radiographs. Five incremental Cox models were developed using clinical, biochemical, nursing/perioperative, radiographic, and surgical variables. LASSO was used for feature selection, followed by multivariable Cox regression. Internal validation was performed using 1,000 bootstrap resamples, and external validation was conducted in an independent geographic cohort.</p> Results <p>The 2-year incidence of structural PTOA was 24.0% (145/605) in the training cohort and 29.0% (60/207) in the validation cohort. Fourteen variables entered the full multivariable Cox model, and 11 independent predictors were retained for the final parsimonious model. The final comprehensive model showed the best performance, with an apparent C-index of 0.892, a bootstrap-corrected C-index of 0.887, and an external validation C-index of 0.865. Relative to the postoperative 3-month AOFAS score as a clinically relevant reference comparator, the comprehensive model showed higher predictive performance, with a continuous net reclassification improvement of 0.785 and an integrated discrimination improvement of 0.285. Time-dependent ROC analysis demonstrated favorable discrimination at 6, 12, and 24 months in both cohorts. Calibration and decision curve analyses also supported good agreement and clinical utility.</p> Conclusions <p>A prospective, multi-source Cox prediction model for structural PTOA after ankle fracture surgery was successfully developed and externally validated. The final 11-variable model demonstrated good discrimination, robust validity, and clear incremental value over traditional early postoperative clinical evaluation indicators, supporting its potential use for individualized risk stratification after ankle fracture surgery.</p>