We assessed whether heritable thrombophilia was more common in cases with symptomatic venous thromboembolism (VTE) after total hip replacement (THA) than among asymptomatic controls without VTE. After THA, 20 cases with deep venous thrombosis (DVT) documented by magnetic resonance venogram (MRV), and 23 with pulmonary embolism (PE) documented by ventilation/perfusion or spiral CT scan, were compared to 43 controls without VTE, matching cases to controls by age, gender, BMI, hip diagnosis, clinical predisposing factors, and VTE prophylaxis. Five of 42 cases (12%) and 0/43 controls (0%) had antithrombin III deficiency (ATIII) (< 75%) (p = .026). Nine of 42 cases (21%) and 2/43 controls (4.7%) had protein C deficiency (< 70%) (p = .021). Ten of 43 cases (9 heterozygous, 1 homozygous) (23%) and 1/43 controls (heterozygous) (2%) had the prothrombin gene mutation (PTG) (p = .004). VTE cases were more likely to have ≥ 1 abnormality of ATIII, protein C, or PTG (21/42 [50%] vs 3/43 [7%]) controls (p<0.0001), with sensitivity 50% and specificity 93% distinguishing cases from controls. For our 1769 cohort prevalence of VTE (2%), the predictive value of a positive test (≥ 1 abnormality of ATIII, protein C, PTG) was 12.8% and for a negative test 98.9%. ATIII deficiency had 11.9% sensitivity and 100% specificity distinguishing cases from controls; the predictive value of a positive test for ATIII deficiency was 100%, the predictive value of a negative test was 98.2%. The PTG mutation had 23.3% sensitivity and 97.7% specificity distinguishing cases from controls; the predictive value of a positive test was 16.9%, the predictive value of a negative test was 98.4%. Deficiencies of ATIII (r = .25, p = .02), protein C (r = .25, p = .021), and PTG (r = .31, p = .003) correlated with postoperative VTE. Having ≥ 1 abnormality of ATIII, protein C, or PTG correlated with VTE status, r = 0.48, p<.0001. Cases with VTE after THA were more likely than controls to have heritable thrombophilia (ATIII or protein C deficiency, PTG homo-heterozygosity). Pre-THA screening for these 3 heritable thrombophilias should improve identification of cases with reduced risk of VTE, who may only need mild thromboprophylaxis, and those with heritable thrombophilia in whom prophylaxis should be more aggressive.