Elderly patients are particularly vulnerable to adverse drug events. This randomized trial used a decision support system coupled with computerized provider order entry to target prescribing of potentially inappropriate medications to elderly patients in an urban emergency department. Physicians who received alerts warning them of a drug's potential adverse effects were significantly less likely to prescribe potentially harmful medications. Although prior studies of computerized reminders have found that physicians frequently ignore reminders, in this study decision support alerts were accepted nearly half the time, and alerts were generally rejected for valid reasons (for example, the patient had tolerated the medication previously). The challenges of implementing effective medication decision support systems are discussed in an AHRQ WebM&M perspective.