Objectives: The objectives of this study were (1) to investigate the effect of nurse training on the use of potentially harmful medications; and (2) to explore the effect of nurse training on residents health-related quality of life (HRQoL), health service utilization, and mortality. Design: A randomized controlled trial. Setting and participants: In total, 227 residents in 20 wards of assisted living facilities in Helsinki were recruited. The 20 wards were randomized into those in which (1) staff received two 4-hour training sessions on appropriate medication treatment (intervention group), and (2) staff received no additional training and continued to provide routine care (control group). Intervention: Two 4-hour interactive training sessions for nursing staff based on constructive learning theory to recognize potentially harmful medications and corresponding adverse drug events. Measurements: Use of potentially harmful medications, HRQoL assessed using the 15 dimensional instrument of health-related quality of life, health service utilization, and mortality assessed at baseline, and 6 and 12 months. Results: During the 12-month follow-up, the mean number of potentially harmful medications decreased in the intervention wards [-0.43, 95 confidence interval (CI)-0.71 to-0.15] but remained constant in the control wards (+0.11, 95 CI-0.09 to+0.31) (. P= .004, adjusted for age, sex, and comorbidities). HRQoL declined more slowly in the intervention wards (-0.038 (95 CI-0.054 to-0.022) than in the control wards (-0.072 (95 CI-0.089 to-0.055) (. P= .005, adjusted for age, sex, and comorbidities). Residents of the intervention wards had significantly less hospital days (1.4 days/person/year, 95 CI 1.2-1.6) than in the control wards (2.3 days/person/year; 95 CI 2.1-2.7) (relative risk 0.60, 95 CI 0.49-0.75, P <.001, adjusted for age, sex, and comorbidities). Conclusions: Activating learning methods directed at nurses in charge of comprehensive care can reduce the use of harmful medications, maintain HRQoL, and reduce hospitalization in residents of assisted living facilities.