OBJECTIVES: To assess the clinical and economic burden of major bleeding in abdominal surgery patients. METHODS: A retrospective study (January 1, 2005 to December 31, 2007) was conducted using a medical claims database. Patients included in the study were admitted to the hospital with abdominal surgery as their primary procedure. Patients' demographic, clinical and discharge statuses were compared using Chi-square testing and standardized differences. Risk-adjusted health care visits and costs were estimated using the General Linear Model (GLM). Potential risk factors for venous thromboembolism (VTE) events were selected using the Cox Proportional Hazard Regression Model. RESULTS: In patients identified with abdominal surgery (n=49,355), 773 (1.57%) suffered major bleeding in the 6-month follow-up period. Compared with patients who did not suffer major bleeding, patients who did were more likely to be older, have higher Charlson Comorbidity Index (CCI) scores and have other comorbid conditions such as cancer. The percentage of patients who had baseline emergency room (ER) visits was also higher in the major bleeding group. After risk-adjustment for pre-specified covariates, inpatient ($21,573 vs. $10,954), outpatient ($12,891 vs. $7,852) and pharmacy costs ($2,025 vs. $1,901) were higher for patients who suffered major bleeding. In addition, patients with major bleeding events had higher readmission rates (0.11% vs. 0.03%) during the follow-up period. CONCLUSIONS: Since the health care costs of patients with major bleeding events were significantly higher than those of patients without, it is important for individual hospitals to improve major bleeding prophylaxis therapy.