Objectives To assess the association between angiotensin converting enzyme inhibitors (ACEis) and improvements in the physical function of older adults in response to chronic exercise training. Design Secondary analysis of the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study, a multisite randomized clinical trial to evaluate the effects of chronic exercise on the physical function of older adults at risk for mobility disability. Setting Four academic research centers within the United States. Participants Four hundred twenty-four individuals aged 70 to 89 with mild to moderate functional impairments categorized for this analysis as ACEi users, users of other antihypertensive drugs, or antihypertensive nonusers. Intervention A 12-month intervention of structured physical activity (PA) or health education promoting successful aging (SA). Measurements Change in walking speed during a 400-m test and performance on a battery of short-duration mobility tasks (Short Physical Performance Battery (SPPB)). Results Physical activity significantly improved the adjusted walking speed of ACEi users (P <.001) but did not of nonusers. PA improved the adjusted SPPB score of ACEi users (P <.001) and of persons who used other antihypertensive drugs (P =.005) but not of antihypertensive nonusers (P =.91).The percentage of ACEi users deriving clinically significant benefit from exercise training for walking speed (30%) and SPPB score (48%) was dramatically higher than for nonusers (14% and 12%, respectively). Conclusion For older adults at risk for disability, exercise-derived improvements in physical function were greater for ACEi users than users of other antihypertensive drugs and antihypertensive nonusers. © 2012, The American Geriatrics Society.