OBJECTIVES: Hemophilia patients frequently experience joint bleeding, resulting in persistent pain and arthropathy. The objective of this study was to determine drivers of total and hemophilia-related costs among hemophilia patients with joint pain. METHODS: InVision™ Data Mart (OptumInsight Life Sciences, 1/2005-3/2009) was used to identify male patients with hemophilia A/B (ICD-09 286.0 and 286.1) who were treated with FVIII/FIX/bypassing agent and had ≥ 2 years of continuous enrollment from index. Patients were stratified into severe joint pain (SJP), ≥ 2 joint pain claims (ICD-9 713, 715, 716, 718, 719, 727) 12 months pre or 6 months post index, and minimal joint pain (MJP), < 2 pain claims. Cohorts were matched on age, treatment type and Charlson comorbidity scores via propensity scoring. Random forest analysis informed covariate selection for log-transformed linear regression models. Covariate selection was further refined based on variance inflation, variable significance and medical relevance. RESULTS: A total of 284 patients (142 SJP, 142 MJP); mean age=30 years were identified. Mean (median) total cost of all patients was $630K ($248K) over a 2-year period but were significantly higher for SJP- $917K compared to MJP- $354K (p<0.01). Hemophilia therapy was the main driver of total patient cost (p<0.0001). Home health visits (p<0.0001), hemophilia-related hospital visits (p<0.0001) and age (p<0.01) were also significant drivers of SJP costs. Removal of covariates measuring factor therapy or claims with hemophilia diagnoses showed that joint pain claims (p<0.01), injectible medications (p<0.01), Charlson Comorbidity Index  (p<0.01), non-hemophilia lab tests (p<0.01), anti-infective medications (p<0.01), and age (p<0.001) were significantly related to total patient cost. CONCLUSIONS: The treatment of joint pain marks significantly higher hemophilia costs, however, some of these differences may be attributed to hemophilia severity (not coded within ICD-9). Modification of ICD-9 codes may help understand economics among hemophilia patients in the future.