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We studied the efficacy and safety of an investigational enoxaparin regimen, 1.5 mg/kg once daily, as a bridge to warfarin for the outpatient treatment of acute venous thromboembolism. We undertook a case-control design. We enrolled 40 acute venous thromboembolism cases prospectively and matched them by age, gender, and location of venous thromboembolism to 80 previously treated controls. All controls had received enoxaparin 1 mg/kg twice daily. The primary end point was recurrent venous thromboembolism. We followed the cases for 30 days. We discontinued enoxaparin after we achieved the target international normalized ratio between 2.0 and 3.0. One case (2.9%) and three controls (3.8%) had recurrent venous thromboembolic events (P = 1.00). There were no major bleeding complications in the case group, compared to 3 (3.8%) in the control group (P = .55). Once daily enoxaparin, 1.5 mg/kg, as a bridge to warfarin was as effective with a similar safety profile as twice daily enoxaparin, 1mg/kg, for initial treatment of acute venous thromboembolism in the outpatient setting. This case-control study provides the rationale for undertaking a randomized controlled trial comparing enoxaparin 1.5 mg/kg once daily versus enoxaparin 1.0 mg/kg twice daily as a bridge to warfarin in outpatients with acute venous thromboembolism.