Background: Venous thromboembolic disease in the form of deep venous thrombosis and pulmonary embolism is a major risk after a total hip arthroplasty. Enoxaparin, a low-molecular-weight heparin, has been shown to reduce the prevalence of deep venous thrombosis after total hip arthroplasty. Warfarin, an orally administered anticoagulant, has been used historically to reduce the risk of deep venous thrombosis after total hip arthroplasty.Methods: We compared enoxaparin and adjusted-dose warfarin with respect to their safety and their efficacy in the prevention of clinically important venous thromboembolic disease, defined as distal or proximal deep venous thrombosis or pulmonary embolism, or both, during hospitalization after total hip arthroplasty. We also evaluated the prevalence of complications and mortality from venous thromboembolic disease within three months after discharge.Results: Three thousand and eleven patients at 156 centers were randomly assigned to prophylactic treatment with injection of enoxaparin or oral administration of adjusted-dose warfarin during hospitalization. During the study, fifty-five (3.6 percent) of the 1516 patients who were managed with enoxaparin and fifty-six (3.7 percent) of the 1495 patients who were managed with warfarin had venous thromboembolic disease. Twenty-one patients (0.7 percent), which included four (0.3 percent) of those managed with enoxaparin and seventeen (1.1 percent) of those managed with warfarin (p = 0.0083), had venous thromboembolic disease during hospitalization. After discharge from the hospital, venous thromboembolic disease developed in ninety patients (3.0 percent): fifty-one (3.4 percent) of those managed with enoxaparin and thirty-nine (2.6 percent) of those managed with warfarin. One patient who had been managed with enoxaparin died because of a pulmonary embolism, which was confirmed at autopsy. Three additional patients (one who had been managed with enoxaparin and two who had been managed with warfarin) died, and the deaths were attributed to venous thromboembolic disease; however, no autopsies were performed. Twenty-six patients (0.9 percent) (eighteen managed with enoxaparin and eight managed with warfarin) had clinically important bleeding.Conclusions: Inpatient programs providing treatment with either enoxaparin (thirty milligrams every twelve hours) or adjusted-dose warfarin for a mean of 7.3 days afforded protection against venous thromboembolic disease, with overall rates of morbidity and mortality of 3.7 and 0.6 percent, respectively, and a very low rate of major bleeding complications (0.9 percent) for three months after total hip arthroplasty. During hospitalization, the patients managed with enoxaparin had a lower rate of venous thromboembolic disease than those managed with adjusted-dose warfarin (p = 0.0083). This benefit was lost after the medication was discontinued, with no difference in the prevalences of venous thromboembolic disease between the two groups at three months after discharge from the hospital.