Objective: Aspirin use may negatively interact with the effect of ACE inhibitors in treating heart failure. Hence, we sought to determine whether aspirin increases the risk of heart failure hospitalizations in non-elderly CHF patients on ACE Inhibitors. Methods: A retrospective analysis of the 2001 Georgia Medicaid claims data was performed. Patients between 18-64 years of age who received a diagnosis of CHF (ICD-9 CM= 428.XX) and filled at least one prescription for ACE Inhibitors between January 1, 2001 and June 30, 2001 were included in the study. Among these patients, those receiving aspirin were classified as the exposed group and patients not receiving aspirin were classified as the unexposed group. Hospitalization due to heart failure was assessed between July 1, 2001 and December 31, 2001. Multi-variable logistic regression provided adjusted estimates of the aspirin effect, with nonusers as the reference group, after controlling for demographic factors, co-morbidities and co-medications. Results: One thousand four hundred fourteen patients were identified. The total number of aspirin users was 178 (12.58%). Average age was 51.36 years and most patients were females (66.5%). Also, most of the selected patients were African Americans(57.1%). The unadjusted odds ratio for exposure to aspirin was 1.798 (95% CI 1.097-2.896) and the adjusted odds ratio was 1.782 (95% CI 1.074-3.009). Conclusion: Aspirin use was associated with a greater risk of hospitalization due to HF in patients taking ACE Inhibitors. Hence, even in non-elderly CHF patients, a caution should be exercised when prescribing aspirin concomitantly with ACE inhibitors.