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Background: Ankle fractures are among the most common injuries treated by orthopaedic surgeons. The purpose of the present investigation was to examine the risks of complications after open reduction and internal fixation of ankle fractures in a large population-based study.Methods: With use of California's discharge database, we identified 57,183 patients who had undergone open reduction and internal fixation of a lateral malleolar, bimalleolar, or trimalleolar ankle fracture as inpatients in the years 1995 through 2005. Short-term complications were examined on the basis of the rates of readmission within ninety days after discharge. The intermediate-term rate of reoperation for ankle fusion or arthroplasty was also analyzed. Logistic regression and proportional hazard regression models were used to determine the strength of the relationships between the rates of complications and fracture type, patient demographics and comorbidities, and hospital characteristics.Results: The overall rate of short-term complications was low, including the rates of pulmonary embolism (0.34%), mortality (1.07%), wound infection (1.44%), amputation (0.16%), and revision open reduction and internal fixation (0.82%). The intermediate-term rates of reoperation were also low, with ankle fusion or ankle replacement being performed in 0.96% of the patients who were observed for five years. Open fractures, age, and medical comorbidities were significant predictors of short-term complications. The presence of complicated diabetes was a particularly strong predictor (odds ratio, 2.30; p < 0.001), as was peripheral vascular disease (odds ratio, 1.65; p < 0.001). The intermediate-term rate of reoperation for ankle fusion or replacement was higher in patients with trimalleolar fractures (hazard ratio, 2.07; p < 0.001) and open fractures (hazard ratio, 5.29; p < 0.001). Treatment at a low-volume hospital was not significantly associated with either the aggregate risk of short-term complications or the risk of intermediate-term reoperation.Conclusions: By analyzing a large, diverse patient population, the present study clarifies the risks associated with open reduction and internal fixation of ankle fractures. Open injury, diabetes, and peripheral vascular disease were strong risk factors predicting a complicated short-term postoperative course. Fracture type was a strong predictor of reoperation for ankle fusion or replacement. Hospital volume did not play a significant role in the rates of short-term or intermediate-term complications.Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.