OBJECTIVES: The objectives were to determine the comparative effectiveness of Angiontensin II receptor blockers (ARB) and Angiotensin converting enzyme Inhibitors (ACEI) in patients with heart failure (HF), and to determine comparative effectiveness of individual drugs within classes - ACEIs and ARBs. METHODS: A retrospective national cohort of Veterans Affairs patients with HF from 1997 to 2002 was employed. Exposure to ARB therapy or ACEI therapy was seen in 2002. Mortality as outcome was assessed within one year of follow-up. Multivariate Cox proportional hazards regression and propensity scoring techniques were employed for data analysis, adjusting for 45 patient risk factors including socio-demographics, co-morbidities, co-medications and severity of illness.  RESULTS: Out of a total cohort of 299,462 patients, 200,552 patients were on either ACEIs or ARBs. 187,478 patients were taking ACEIs and 25,987 were taking ARBs. There was no significant difference in reduction of risk of mortality with use of ARBs versus ACEIs (HR 0.955, 95% CI: 0.907-1.006). Results from stratification using propensity score analysis also suggest the same. Patients were stratified into 5 groups based on propensity to receive ARB. Proportion of patients that died was not significantly different for ACEI and ARB in four out of the five groups. Among ACEIs, Enalapril (HR 0.715, 95% CI: 0.584-0.876), Fosinopril (HR 0.778, 95% CI: 0.729-0.830) and Lisinopril (HR 0.784, 95% CI: 0.740-0.831) were significantly better than Captopril in reducing risk of mortality. Among ARBs, Candesartan (HR 0.847, 95% CI: 0.751-0.994) and Irbesartan (HR 0.892, 95% CI: 0.795-1.00) were significantly better than Losartan in reducing risk of mortality.   CONCLUSIONS: Results from the study suggest that ARBs are equally effective as ACEIs in reducing risk of mortality in heart failure patients and there are significant differences in effectiveness of individual drugs within ACEIs and ARBs in reducing risk of mortality in heart failure.