Objective To review the diagnostic accuracy of the Ottawa Ankle and Midfoot Rules and explore if clinical features and/or methodological quality of the study influence diagnostic accuracy estimates. Design Systematic review with meta-analysis. Data sources MEDLINE, EMBASE, CINAHL, SPORTDiscus and Cochrane Library. Eligibility criteria for selecting studies Primary diagnostic studies reporting the accuracy of the Rules in people with ankle and/or midfoot injury were retrieved. Diagnostic accuracy estimates, overall and for subgroups (patient's age, profession of the assessor and setting of application), were made. Sensitivity analyses included studies with a low risk of bias and studies where all patients received radiographs. Results 66 studies were included. Ankle and Midfoot Rules presented similar accuracies, which were homogeneous and high for sensitivity and negative likelihood ratios and poor and heterogeneous for specificity and positive likelihood ratios (mean, 95% CI pooled sensitivity of Ankle Rules: 99.4%, 97.9% to 99.8%; specificity: 35.3%, 28.8% to 42.3%). Sensitivity of the Ankle Rules was higher in adults than in children, but the profession of the assessor did not appear to influence accuracy. Specificity was higher for Midfoot than for Ankle Rules. There were not enough studies to allow comparison according to setting of application. Studies with a low risk of bias and where all patients received radiographs provided lower accuracy estimates. Specificity heterogeneity was not explained by assessor training, use of imaging in all patients and low risk of bias. Conclusions Study features and the methodological quality influence estimates of the diagnostic accuracy of the Ottawa Ankle and Midfoot Rules.