In the outpatient setting, patients frequently experience adverse events between clinician visits, and many of these may go undetected. This randomized controlled trial sought to evaluate a novel method of engaging patients in safety in order to identify and prevent adverse drug events (ADEs) in outpatients. Patients who were enrolled in an online patient portal (which allowed them to view their own laboratory results and communicate directly with their clinicians) were randomized to be sent automated queries after receiving a new prescription. The queries confirmed whether the prescription was filled and asked questions to detect potential ADEs. Nearly half of the intervention group patients responded to a query and many prescription problems were discovered, but the overall rate of ADEs was no different than the control group (which was enrolled in the portal but did not receive the medication safety messages).