OBJECTIVE: To evaluate the effect of a medication therapy management (MTM) intervention on adverse drug events (ADEs), health care visits, and drug-related problems (DRPs). DESIGN: Randomized, controlled, clinical trial. SETTING: Academic medical center community pharmacies and family medicine clinics at three U.S. sites between December 2007 and January 2010 PATIENTS: Individuals aged 65 years or older with three or more chronic illnesses, six or more prescription medications, and at risk for a DRP. INTERVENTION: At 0 and 3 months, pharmacists conducted comprehensive medication reviews and screened for and resolved DRPs through patient education and recommendations to physicians. MAIN OUTCOME MEASURES: Frequency of ADEs reported by patients and confirmed by clinical algorithm, health care visits at 3 and 6 months, and number of DRPs, pharmacist recommendations, and medication discrepancies. RESULTS: 637 participants enrolled. No differences were observed in potential ADEs or health care visits among the usual care and MTM groups. DRPs declined in both MTM intervention groups over time. Physicians responded to 54.6% of pharmacist recommendations. Enhanced MTM patients had fewer medication list discrepancies than basic MTM patients (33.8% vs. 47.1%, P < 0.001). CONCLUSION: This specific design of MTM was associated with reduced DRPs but did not reduce potential ADEs or health care visits.