OBJECTIVES: To assess the effect of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) on health related quality of life (HRQoL) in patients with hypertension and diabetes. METHODS: Medical Expenditure Panel Survey (MEPS) 2002-2007 was used for the study. Each panel in MEPS followed patients for about 2 years with data collected in five rounds of 4 to 5 months each. HRQoL was measured using the physical and mental component scores of the SF-12 quality of life instrument. Baseline HRQoL was measured at the end of round 2. Incident utilization for ACEI and ARB was determined during round 3 or 4, and outcome HRQoL was measured at the end of round 4. Analysis was performed on two populations: patients utilizing either ACEI or ARB vs. neither; and patients utilizing ARB vs. ACEI. Multiple linear regression models were performed to test the unique effect of ACEI and ARB on the physical and mental component of HRQoL while controlling for baseline HRQoL, comorbidities, comedications, demographic and socio-economic factors. RESULTS: Overall 60% of patients received either ACEI or ARB. Of the 20% of these who were incident users of ACEI/ARB, ACEI was utilized by 65% of the patients. Multiple linear regression models did not reveal any statistically significant effect of using ACEI or ARB vs neither on the physical (p = 0.27) or mental (p = 0.47) component of HRQoL. Similarly, using ACEI versus ARB did not have any statistically significant effect on the physical (p = 0.20) and mental (p = 0.66) components of HRQoL. CONCLUSIONS: ACEI and ARB, now regarded as quality of care measures for patients with concomitant hypertension and diabetes, did not seem to affect patients’ HRQoL. More research is needed to evaluate the long term consequences of ACEI and ARB use.