Background The prevalence of deep vein thrombosis as demonstrated by routine venography in patients with distal lower-extremity injury requiring cast immobilization or surgery is 10% to 40%. These deep vein thromboses are usually asymptomatic and distal, and the need for thromboprophylaxis in these patients is not known. Methods We conducted a multicenter prospective cohort study to define the prevalence of symptomatic venous thromboembolism in patients with a tibial, fibular, or ankle fracture (treated nonoperatively) or a patellar or foot fracture (treated operatively or conservatively). Consecutive patients were enrolled at five Ontario, Canada, hospitals within ninety-six hours after injury, and they were followed with a telephone interview at two, six, and twelve weeks. Thromboprophylaxis was not allowed. Suspected venous thromboembolism was investigated in a standardized manner. Results From August 2002 to June 2005, 1200 patients were enrolled, and a three-month follow-up was completed for 98% of them. Eighty-two percent of the patients were treated with cast or splint immobilization for an average (and standard deviation) of 42±32 days. Overall, seven patients (0.6%; 95% confidence interval [CI] = 0.2% to 1.2%) had symptomatic, objectively confirmed venous thromboembolism. Two of them had proximal deep vein thrombosis; three, calf deep vein thrombosis; and two, pulmonary embolism. There were no fatal pulmonary emboli. Conclusions Symptomatic venous thromboembolism is an infrequent complication after fractures of the distal part of the lower limb requiring cast immobilization and managed without thromboprophylaxis. Given these estimates of symptomatic venous thromboembolism, the risk-benefit ratio and cost-effectiveness of routine anticoagulant prophylaxis are unlikely to be favorable for these patients. Level of Evidence Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.