BACKGROUND: Legg-Perthes disease is associated with ischemia of the capital femoral epiphysis in children. Thrombophilia has been implicated as a potential cause of the condition, and screening of patients with Legg-Perthes disease for thrombophilia has been recommended. We analyzed the value of screening for inherited thrombophilia in patients with Legg-Perthes disease by examining the association between Legg-Perthes disease and abnormalities in the thrombotic pathway. METHODS: A random series of consecutive patients with Legg-Perthes disease were prospectively enrolled in this study. Assays for the detection of factor-V Leiden mutation and the plasma concentrations of protein C, protein S, antithrombin III, and lipoprotein (a) were performed on plasma samples from children with Legg-Perthes disease, and the results were compared with those for pooled plasma from normal controls. Plasma concentrations below the 95% midrange of the control values were classified as protein deficiencies. The estimated population frequency of each coagulation abnormality was compared with the proportion of the study group with the corresponding abnormality. RESULTS: The proportion of abnormalities observed in the study group did not differ from the estimated population frequency for protein C, protein S, antithrombin III, or factor-V Leiden mutation. A lipoprotein (a) level of >30 mg/dL (>1.07 micro mol/L) was found in 16% of the study group. CONCLUSIONS: Our data do not suggest that thrombotic diatheses due to deficiency of protein C, protein S, or antithrombin III or due to factor-V Leiden mutation are major causes of Legg-Perthes disease. The elevated levels of lipoprotein (a) in children with Legg-Perthes disease suggest that they may be at risk for atherosclerosis as adults.