Background: Despite the national attention being given to the problem of medication safety, little attention has been paid to the medication problems that are encountered by older patients who are receiving care across settings. The objective of this study was to determine the prevalence and contributing factors associated with posthospital medication discrepancies. Methods: The study population consisted of community-dwelling adults aged 65 years and older admitted to the hospital with 1 of 9 selected conditions (n = 375). A geriatric nurse practitioner performed a comprehensive medication assessment in the patient’s home within 24 to 72 hours after institutional discharge. The assessment focused on what older patients reported taking in comparison with the prehospital medication regimen and the posthospital medication regimen. Prevalence and types of medication discrepancies were categorized using the Medication Discrepancy Tool. Results: A total of 14.1% of patients experienced 1 or more medication discrepancies. Using the Medication Discrepancy Tool, 50.8% of identified contributing factors for discrepancies were categorized as patient-associated, and 49.2% were categorized as system-associated. Five medication classes accounted for half of all medication discrepancies. Medication discrepancies were associated with the total number of medications taken and the presence of congestive heart failure. A total of 14.3% of the patients who experienced medication discrepancies were rehospitalized at 30 days compared with 6.1% of the patients who did not experience a discrepancy (P = .04). Conclusions: A significant percentage of older patients experienced medication discrepancies after making the transition from hospital to home. Both patient-associated and system-associated solutions may be needed to ensure medication safety during this vulnerable period.