Background: Enoxaparin, a low-molecular-weight heparin administered to hospitalized patients once or twice daily, has shown efficacy and safety equivalent to unfractionated heparin in the treatment of acute venous thromboembolic disease. Although the cost of either enoxaparin regimen is greater than that of unfractionated heparin, the overall cost of care for each of these 3 treatment strategies is unknown. Methods: A cost minimization analysis of a 3-month, partially blinded, randomized, controlled efficacy and safety trial of anticoagulant therapy for deep vein thrombosis. Three hundred thirty-nine hospitalized patients with symptomatic lower extremity deep vein thrombosis were randomly assigned to initial therapy with subcutaneous enoxaparin either once (n = 112) or twice (n = 123) daily, or with dose-adjusted intravenous unfractionated heparin (n = 104), followed by, long-term oral anticoagulant therapy. Estimated 1997 total cost from a third-party payer perspective for the 3-month episode of care was calculated by assigning standard unit costs to counts of medical resources used by each patient in the clinical trial. Results: Average total cost for the 3-month episode of care was similar across all 3 treatment regimens: once-daily dose of enoxaparin, $12166 (95% confidence interval [CI], $10744-$13588); twice-daily dose of enoxaparin, $11558 (95% CI, $10201-$12915); and unfractionated heparin, $12146 (95% CI, $10670-$12622). Bootstrapped estimates and sensitivity analyses did not significantly change findings. Conclusions: There was no significant difference in the overall cost for the 3-month episode of care for patients treated with either enoxaparin or unfractionated heparin. Additional acquisition costs for anticoagulant medication among patients treated with enoxaparin were offset by savings associated with lower incidence of hospital readmission and shorter duration of venous thromboembolism-related readmissions.