Objective: To assess 12-month healthcare resource utilization and costs associated with upper gastrointestinal (UGI) bleeding events. Methods: Patients hospitalized with a UGI bleeding event were identified in US national health-plan claims data (1999-2003) and propensity matched to control patients without UGI bleeding in the same health plan. Matching criteria included age, gender, index date, Charlson Comorbidity Index score, geographic region, and prior medical utilization. Results: A total of 9,033 UGI-bleed patients and 579,018 control patients met the inclusion criteria, yielding 4,651 matched pairs. After matching, differences between the UGI bleed and general population cohorts remained for office visits, ER visits, and ER costs during the 6-month baseline period prior to the index date. During the 12 months following the index date, both UGI-related healthcare utilization and total healthcare, medical, and pharmacy costs incurred by the UGI-bleed cohort were significantly greater (p<0.0001) than those incurred by the general population cohort (mean of $20,405 vs. 3,652), even after excluding the initial hospitalization costs (mean of $11,228 vs. 3,652). Costs were primarily due to inpatient hospitalizations (mean of $13,059 for the UGI-bleed cohort vs. $729 for the general population cohort) and ambulatory services (mean of $4,037 for the UGI-bleed cohort vs. $1,537 for the general population cohort). Sixteen percent of the UGI-bleed cohort had a GI-related hospitalization, and about 40% of total costs occurred after the initial hospitalization. Conclusions: Patients with UGI bleeds experienced significantly higher (p<0.0001) 12-month health-resource utilization and costs than patients without UGI bleeds. This study provides empirical evidence of the long-term economic burden associated with UGI bleeding. Interpretation of the results should take into account the lack of available information in claims data that could have an effect on study outcomes, such as particular clinical and disease-specific parameters that are not mitigated by propensity score and comorbidity index matching. In addition, this study is limited by the intensive demographic matching that was done between the two cohorts, which may have eliminated the sickest UGI patients and the healthiest general health-plan population patients. © 2010 Informa UK Ltd.