Background Medication discrepancies may occur at transitions in care and negatively impact patient outcomes. Objective To determine if involving clinical pharmacists in hospital care, medication reconciliation and discharge medication plan communication can reduce medication discrepancies with a prospective, randomized, blinded, controlled trial. Setting A large, tertiary care, academic medical center. Method The intervention consisted of clinical pharmacist medication reconciliation, patient education and improved communication of the discharge medication plan, as devised by the hospital physician and care team, to primary care physicians and community pharmacists. Medication discrepancies were identified by blinded research pharmacists who reviewed primary care physician and pharmacy records at discharge through 90 days post-discharge to create 30-day and 90-day medication lists. Main outcome measure: Rate of medication discrepancies compared across groups. Results A total of 592 subjects from internal medicine, family medicine, cardiology and orthopedic services were evaluated for this study. Clinically important medication discrepancies in the primary care physician record were different between groups 30 days after hospital discharge following a clinical pharmacist's intervention. The mean number of medication discrepancies per patient for the enhanced group being nearly half the number in the control group. However, this effect did not persist to 90 days post-discharge and did not extend to community pharmacy records. Conclusion The present study demonstrates the involvement of pharmacists in hospital care, medication reconciliation and discharge medication plan communication may affect the quality of the outpatient medical record.