Two hundred forty consecutive patients admitted for operative treatment of an open fracture of the arm or leg were followed up prospectively for the development of fracture infection. The independent risk of fracture infection was increased in patients with grade IIIB or IIIC fractures, internal or external fixation, lower-leg fracture, any blood transfusion, or injuries resulting from motorcycle accidents or motor vehicle-pedestrian accidents. By stepwise multivariate logistic regression, the most significant risk factors were the grade of the fracture, internal or external fixation, and fractures of the lower leg. These risk factors all represent local wound characteristics, and we conclude that the most important actions by the surgeon to prevent infection involve local wound care. There was no relation between the timing of antibiotic administration or duration of antibiotic therapy and infection risk.