Bolus urokinase (Abbokinase ) is effective for initial treatment of deep venous thrombosis but is associated with a high rate of rigors. This randomized controlled trial was undertaken among patients with deep venous thrombosis to evaluate the efficacy and safety of a novel thrombolytic agent, recombinant urokinase (rUK), administered as three bolus infusions of 1 million U over a 24-hour period versus heparin alone. Of 361 patients with DVT screened, 17 (5%) were enrolled. Recent surgery was the most common reason for exclusion (n = 113, 31%). Images of the patients were obtained at baseline, 24 to 48 hours after randomization, and before hospital discharge. Two patients in each treatment group had minor clot progression. One patient in the heparin group had no change; all other patients showed mild (< 50%; n = 5 in each group) or moderate (> 50%; n = 1 in each group) improvement. No bleeding complications or rigors developed in patients randomized to rUK. Mean bleeding times among patients given rUK were not significantly different from mean values of patients given heparin at any of the measured time points available for comparison (331 vs 387 seconds at baseline and 381 vs 416 seconds at 24 hours). However, mean fibrinogen levels declined with successive urokinase boluses and were significantly lower than levels in patients treated with heparin at 24 (233 mg/dl vs 466 mg/dl, p = 0.01) and 48 hours (270 mg/dl vs 474 mg/dl, p = 0.02). Although bolus rUK had a favorable safety profile, rUK was no more effective than heparin in achieving clot lysis at the doses used in this trial.