In a prospective study of nursing home residents, we found adverse drug events (ADEs) to be common, serious, and often preventable. To direct prevention efforts at high-risk residents, information is needed on resident-level risk factors. Case-control study nested within a prospective study of ADEs among residents in 18 nursing homes. For each ADE, we randomly selected a control from the same home. Data were abstracted from medical records on functional status, medical conditions, and medication use. Adverse drug events were identified in 410 nursing home residents. Independent risk factors included being a new resident (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.5-5.2) and taking anti-infective medications (OR, 4.0; CI, 2.5-6.2), antipsychotics (OR, 3.2; CI, 2.1-4.9), or antidepressants (OR, 1.5; CI, 1.1-2.3). The number of regularly scheduled medications was associated with increased risk of ADEs; the OR associated with taking 5 to 6 medications was 2.0 (CI, 1.2-3.2); 7 to 8 medications, 2.8 (CI, 1.7-4.7); and 9 or more, 3.3 (CI, 1.9-5.6). Taking supplements or nutrients was associated with lower risk (OR, 0.42; CI, 0.27-0.63). Preventable ADEs occurred in 226 residents. Independent risk factors included taking opioid medications (OR, 6.6; CI, 2.3-19.3), antipsychotics (OR, 4.0; CI, 2.2-7.3), anti-infectives (OR, 3.0; CI, 1.6-5.8), antiepileptics (OR, 2.2; CI, 1.1-4.5), or antidepressants (OR, 2.0; CI, 1.1-3.5). Scores of 5 or higher on the Charlson Comorbidity Index were associated with increased risk of ADEs (OR, 2.6; CI, 1.1-6.0). The number of regularly scheduled medications was also a risk factor: the OR for 7 to 8 medications was 3.2 (CI, 1.4-6.9) and for 9 or more, 2.9 (CI, 1.3-6.8). Residents taking nutrients or supplements were at lower risk (OR, 0.27; CI, 0.14-0.50). It is possible to identify nursing home residents at high risk of having an ADE. Particular attention should be directed at new residents, those with multiple medical conditions, those taking multiple medications, and those taking psychoactive medications, opioids, or anti-infective drugs.