The efficacy and safety of RD heparin, a low-molecular-weight heparin, for the prevention of venous thromboembolic disease among patients managed with an elective total hip or total knee arthroplasty were compared with the efficacy and safety of warfarin in an open-label prospective, multicenter trial. Patients were randomized to receive either a fixed dose of fifty anti-factor-Xa units of RD heparin per kilogram of body weight, administered subcutaneously twice daily, beginning postoperatively; a fixed dose of ninety anti-factor-Xa units of RD heparin per kilogram of body weight, administered subcutaneously once daily, beginning postoperatively; or five milligrams of warfarin, administered orally preoperatively, followed by a daily adjusted dose of warfarin to prolong the prothrombin time ratio to 1.2 to 1.5. The primary measure of efficacy was contrast venography of the treated limb, performed by local radiologists blinded to the type of treatment that had been assigned. Nine hundred and sixty-nine patients had a complete assessment for the presence of deep-vein thrombosis. The over-all rates of venous thromboembolic disease were 16 percent (95 pecent confidence interval, 13 to 21 percent) (fifty-three) for the 328 patients who received RD heparin twice daily, 21 percent (95 percent confidence interval, 17 to 26 percent) (sixty-eight) for the 320 patients who received RD heparin once daily, and 27 percent (95 percent confidence interval, 22 to 32 percent) (eighty-seven) for the 321 patients who received warfarin (p < 0.001 for RD heparin administered twice daily compared with warfarin; p = 0.13 for RD heparin administered once daily compared with warfarin). Compared with warfarin, RD heparin administered twice daily and RD heparin administered once daily reduced the risk of venous thromboembolic disease by 41 percent (95 percent confidence interval, 20 to 56 percent) and 18 percent (95 percent confidence interval, -6 to 37 percent), respectively. The rates of venous thromboembolic disease after 523 total hip arthroplasties were 8, 14, and 14 percent for the patients who received RD heparin twice daily, those who received it once daily, and those who received warfarin (p = 0.07 for RD heparin administered twice daily compared with warfarin; p = 0.82 for RD heparin administered once daily compared with warfarin).(ABSTRACT TRUNCATED AT 400 WORDS)