The only Food and Drug Administration-approved thrombolytic regimen for treatment of deep venous thrombosis (DVT) is a 24- to 72-hour continuous infusion of intravenous streptokinase. This approach to DVT thrombolysis is not entirely satisfactory because of the bleeding complications that may accompany this therapy. In the current study, we treated 27 patients with DVT with a novel dosing regimen of urokinase: 1,000,000 U administered as a 10-minute bolus, with a total of 3 boluses given over approximately 24 hours. Patients were given heparin overnight between bolus urokinase doses. Efficacy was assessed by comparing baseline and prehospital discharge vascular imaging studies, which constituted either venous ultrasound or contrast venography. A vascular-imaging panel of physicians, unaware of the sequence of paired studies, found that 14 patients (52%) had clot lysis (6 slight, 6 moderate and 2 marked), 9 (33%) had no change, and 4 (15%) had more extensive thrombosis after treatment (1 slight, 2 moderate and 1 marked). There were no bleeding complications. At 48 hours after starting urokinase, mean plasma fibrinogen levels had decreased 61% from baseline, and the mean bleeding time had increased 28% from baseline (but remained within the normal range). Because of the promising efficacy and safety that were found in this case series, it is concluded that further testing of bolus urokinase is warranted against anticoagulation alone.