OBJECTIVES There has been an increase in the number of clotting factor (CF) products available in the U.S. in recent years. Thrombotic events (TEs) are serious adverse events that can occur following administration of CFs. The objective of this study is to assess the same-day TE risk following exposure to CF products. METHODS A retrospective cohort study of individuals exposed to CF products during January 2008 through June 2013 was conducted using HealthCore Integrated Research Database (HIRD^SM). CF products were identified by Healthcare Common Procedure Coding System (HCPCS) codes, and TEs were ascertained via ICD-9-CM diagnosis codes. Crude same-day TE rates (per 1,000 persons exposed) were estimated overall, by congenital clotting factor deficiency status and by specific CF products, age, and gender. RESULTS Of 3,801 individuals exposed to CFs, 117 (30.8 per 1,000 persons) had TEs recorded on the same-day as CF exposure. The crude same-day TE rate (per 1,000) was higher for CF users without congenital CF deficiency, 70.2 (102 of 1,452), as compared to those with congenital CF deficiency, 6.4 (15 of 2,349), unadjusted rate ratio of 11.0 (95% CI 6.4-18.9). For individuals without congenital CF deficiency, the crude TE rates (per 1,000) were 15.9 for under 15 years of age, 16.1 for 15 to 44 years, 62.8 for 45 to 64 years, and 160.9 for 65 years and older. The unadjusted same-day TE rates (per 1,000) ranged from 12.8 for Factor VIII to 204.1 for Factor IX complex product(s). Multivariable analyses are underway to control for potential confounders and identify recipient risk factors. CONCLUSIONS The study shows an increased risk of same-day TEs for CF users without congenital CF deficiency and suggests a potentially substantial off-label use of CFs, which needs further investigation. In addition, study findings suggest elevated same-day TE rates for specific CF products with additional multivariable investigation ongoing.