Clinician decision support systems (CDSS) hold great promise as a means of promoting appropriate care, reducing diagnostic errors, and minimizing medication prescribing errors. However, a recent systematic review found that, taken as a whole, decision support systems achieved only small changes in provider behavior. In this study, a custom-designed CDSS that focused on preventing excessive medication dosages was implemented within a computerized provider order entry system, and resulted in a significant reduction in prescribing errors. Clinicians accepted one in four of the CDSS warnings—a seemingly low proportion that is, in fact, much higher than response rates found in many prior studies of drug alert warnings. The system was carefully tailored to be integrated into provider workflow and to provide only patient-specific warnings, factors that likely contributed to its success.