The aim of this study was to evaluate prospectively the clinical short-term outcome of patients with suspected deep venous thrombosis (DVT) and negative duplex investigation and to assess whether it is clinically safe to withhold anticoagulant therapy on the basis of a single negative color duplex examination including the calf veins. The study included a consecutive series of patients with suspected DVT referred for color duplex examination over 1 year. Patients with negative duplex findings (n = 341) were followed up for 3 months clinically and/or by reviewing hospital charts and the official registry of health care and causes of death. In only 1 of the patients was DVT diagnosed following a negative duplex examination. This patient had accentuated symptoms and a thrombus in the peroneal vein was detected at subsequent phlebography. None of the other patients with a negative duplex finding developed signs of, or had treatment initiated for, DVT or pulmonary embolism during the 3-month period after the duplex investigation. Five patients died, but none of the deaths was related to thromboembolism. The results indicate that it is clinically safe to rely on a single negative color duplex examination in patients without any progressing symptoms from the affected limb.