Costs-benefits of 3 strategies to deal with pulmonary emboli (PE) and deep venous thrombosis (DVT) after total hip replacement (THR) in 1769 cases were assessed. Based on examining 23 PE and 20 DVT cases and 43 matched controls, PE-DVT cases were more likely to have ≥ 1 abnormality of antithrombin III, protein C, or the prothrombin gene mutation (21/42 [50%] vs 3/43 [7%]) (p<0.0001), with sensitivity 50% and specificity 93%. Using sensitivity of 50% and specificity of 93%, we compared 3 strategies, no coagulation screening-aspirin-no low molecular weight heparin (LMWH)-no warfarin (W), no coagulation screening-universal LMWH-W, and universal coagulation screening-selective LMWH-W in cases with thrombophilia. We used cost estimates for short-term and for lifetime treatment of PE-DVT. We included costs due to major bleeding on LMWH-W in 3% of cases. We used short-term (˜ 10 days post THR) documented PE (1.5%) (by spiral CT) and DVT (48.5%) (by venogram). We estimated PE and DVT events not detected by the coagulation screening, and PE-DVT despite LMWH, pneumatic compression, or W. With no coagulation screening, aspirin, and no LMWH-W, 27 PE and 858 DVT would be expected, for a cost of $10,692/case. With universal LMWH-W, 3 PE and 313 DVT would be expected on LMWH, 366 DVT with pneumatic compression, and 410 on W, but 53 bleeding cases would occur. Using universal LMWH-W, on LMWH cost was $6,143/case, on W $7,239, and with pneumatic compression $6,743. Using universal coagulation screening and selective LMWH-W in cases with thrombophilia, 15 PE and 634 DVT would be expected; 1265 cases would not get LMWH-W, 38 bleeding events would be avoided, and 45% of PE and 26% of DVT avoided vs no coagulation screening, no LMWH-W. Universal coagulation screening with selective LMWH-W costs $8,630/case for LMWH, $8,930 for compression alone, and $9,178 for W. As our knowledge of thrombophilia-hypofibrinolysis improves, current sensitivity (50%) and specificity (93%) for coagulation screening should improve, allowing more selective LMWH-W for high risk cases, avoiding LMWH-W in cases without coagulation disorders.