OBJECTIVES: Bleeding episodes pose significant economic and quality-of-life (QoL) burdens on persons with hemophilia. This study aims to identify socio-demographic and clinical characteristics associated with annual bleeding frequency (ABF). METHODS: Between 2005-2007 and 2009-2012, the Hemophilia Utilization Group Studies Va and Vb, respectively, recruited hemophilia A or B patients from ten geographically diverse Hemophilia Treatment Centers in the United States. Adult patients or parents of children completed a baseline survey that collected information regarding socio-demographics, clinical characteristics, and treatment patterns. During the two-year observation period, bleeding episodes were collected through regular patient follow-ups. ABF was calculated as the annualized sum of patient-reported bleeding episodes. Two-year drug dispensing information was also recorded and annualized. Multivariable linear regressions were used to assess the association of patient variables with ABF. RESULTS: Of 477 recruited patients, 317 with complete baseline and utilization data and at least three months of patient follow-up were included. Among included patients, 49.8% were children, 39.7% used prophylaxis, and 63.1% had severe hemophilia. Variables significantly associated with ABF included 37 or older vs. 2-9 years of age (p=0.03), married or with a partner (p=0.03), hemophilia B (p=0.09), mild/moderate hemophilia (p=0.01), prophylaxis (p<0.01), human immunodeficiency virus (HIV) (p<0.01), hepatitis C virus (HCV) (p<0.01), and annual factor usage per kilogram of body weight (p<0.01). Among adults, age in years (p=0.07), no insurance vs. public insurance (p=0.04), mild/moderate hemophilia (p=0.01), HIV (p<0.01), HCV (p=0.02), and factor usage (p=0.02) were significantly associated with ABF. Fewer variables had a significant association with ABF for children compared to adults, including prophylaxis (p<0.01) and factor usage (p=0.01). CONCLUSIONS: Variables associated with ABF include socio-demographics, clinical characteristics and factor usage. The preliminary results reinforce the importance of optimizing treatment for individual differences. Future studies should investigate how variations in bleeding outcomes and treatment are associated with healthcare costs.