OBJECTIVES: To assess factors associated with pain and functional capabilities independent of hemophilia-related arthropathy. METHODS: US adults with hemophilia completed patient-reported outcome instruments to assess pain (Brief Pain Inventory, BPI), functional impairment (Hemophilia Activities List, HAL), and quality of life (EQ-5D-5L). Physiotherapists optionally completed joint evaluation (Hemophilia Joint Health Score, HJHS). The association of BPI scores and HAL with HJHS and other covariates was examined using simple regression models and by a multiple regression model where HJHS, age, hemophilia severity, and treatment were included with other covariates having bivariate correlations with BPI/HAL scores (α<0.05) using forward selection. RESULTS: Of 381 adults enrolled, 240 had complete HJHS scores (median age 32, 64% severe hemophilia, 9% hemophilia with inhibitors). In simple regression, higher EQ-5D-5L pain/discomfort score had strong association with worse BPI outcomes, but this association did not remain when adjusted for other covariates. For BPI pain-severity (R-squared=0.422) and BPI pain-interference (R-squared=0.386), the most consistent significant predictors of worse outcomes after adjusting for HJHS were non-employed status, use of opiates, and anxiety/use of anxiolytics. For HAL overall score (R-squared=0.700), the most significant predictors of worse outcomes after adjusting for HJHS were older age, non-employed status, more severe hemophilia (with inhibitor patients as most severe), BPI pain-severity, and higher EQ-5D-5L pain/discomfort. EQ-5D-5L anxiety/depression and use of anxiolytics/antidepressants/opiates were significant in simple regression only. Sensitivity analysis removing hemophilia severity lowered R-squared values for BPI (severity 0.38, interference 0.36) but not for HAL. CONCLUSIONS: Independent of joint status, employment, anxiety, and depression were associated with both pain and functional abilities; pain severity was also associated with functional abilities. The predictive power of the studied covariates was higher for functional outcomes than pain, possibly due to the closer correlation of objective joint status with reported disability, and increased day-to-day variability of pain.