OBJECTIVES: Hemophilia A and B are marked by frequent joint bleeding, resulting in pain and functional impairment. This study aimed to assess the reliability of five PRO instruments in PWH in a non-bleeding state. METHODS: Sequential adult male PWH of any severity (with or without inhibitors) with a history of joint pain or bleeding completed a pain history and five PRO instruments (EQ-5D-5L, Brief Pain Inventory v2 [BPI], SF-36v2, International Physical Activity Questionnaire [IPAQ], and Hemophilia Activities List [HAL]) during routine clinic visits. To assess concordance of individual questionnaire items and correlation of domain/global scores using intraclass correlation coefficient (ICC), initial patients (target 125-150) were approached to complete the PROs at the end of their 3-4 hour visit in a similar non-bleeding state. RESULTS: From October 2013-October 2014, 381 patients enrolled; 164 (88% of initial 187) completed the retest. Median age of retest cohort was 33.9 years (Q1, Q3; 26.9, 46.0). Median time for completion of the initial survey with five PROs was 36.0 minutes and for the retest was 21.0 minutes. Median/mean time between tests was 1.5/1.6 hours. The majority of subjects had hemophilia A (74.4%) and were white-non-Hispanic (72.6%); 48.7% were married, 62.6% had some college or graduate-level education, 80.7% were employed, and 61.0% were overweight or obese. HCV was more common than HIV (49.4% vs 16.5%); 61.0% self-reported arthritis/bone/joint problems. Median/mean test-retest concordance was: EQ-5D-5L, 80.0%/79.1%; BPI, 54.5%/58.9%; SF-36v2, 77.8%/76.4%; IPAQ, 100%/100%; and HAL, 77.4%/75.9%. ICC for test-retest reliability were: EQ-5D-5L Health Index, 0.890; BPI–severity, 0.950; BPI–interference, 0.920; IPAQ total activity, 0.940; SF-36v2 overall health, 0.910; HAL total score, 0.970. CONCLUSIONS: All five PROs are reliable in adult PWH. Therefore, the choice of instrument to be used for research or clinical care should be driven by instrument characteristics other than reliability.