The purpose of this study was to identify and characterize adverse drug events (ADEs) in a primary care setting using an electronic health record (EHR). This prospective, observational study enrolled patients with any medication change who were seen at an outpatient internal medicine clinic. Patients were evaluated for ADEs by EHR review and telephone interview. ADEs were independently assessed for causality, severity, preventability, and ameliorability by a physician and a pharmacist using a grading instrument. There were 1368 unique medication changes for 701 individuals who completed the study (1.95 changes per person). Of the 226 suspected ADEs, 68 (58%) were deemed to be “definite” or “probable” following causality assessment; 21% were preventable and 40% ameliorable. Only 2 ADEs were serious or life-threatening. Compared with prior reports, ADEs in primary care have decreased in frequency and severity, yet the occurrence of preventable and ameliorable ADEs has increased.