PURPOSE: To determine the diagnostic value of venous ultrasonography (US) that includes examination of calf veins in symptomatic patients suspected of having deep venous thrombosis (DVT) of the lower extremities. MATERIALS AND METHODS: A retrospective cohort study of the prevalence of DVT included 977 consecutive patients with possible DVT but without known risk factors for DVT. Color flow and compression US were performed. The outcome was the frequency of overlooked, clinically important DVT after negative initial results from bilateral venous US of above- and below-the-knee veins. Patient records (904 patients), mailed questionnaires (61 patients), and telephone contacts (12 patients) were used to establish a diagnosis of clinically relevant DVT. RESULTS: The prevalence of DVT was 15% (142 of 977), with DVT in 15% (21 of 142) restricted to the below-the-knee veins. Follow-up (median, 34 months) in 835 patients with negative US findings showed one occurrence of venous thrombosis (superficial thrombophlebitis) during the first 3 months of follow-up. Three other cases of venous thrombosis occurred at 17, 18, and 48 months of follow-up but were believed not to be linked to the initial complaint. The incidence of overlooked DVT was 0% (95% CI, 0.0%, 0.4%). CONCLUSION: In patients without risk factors for DVT, a negative venous US study can help exclude the presence of clinically important DVT if the examination includes careful evaluation of the calf veins.