Chronic disease care increasingly involves patients engaging in self-management activities outside of discrete clinical encounters—for example, diabetics must monitor their blood sugars at home. This study used retrospective analysis of data from an interactive telephone-based diabetes self-management system to characterize the types and severity of adverse events occurring between physician visits in a low health literacy patient population. The vast majority of patients experienced at least one adverse event, most of which were considered preventable. Most events were detected by prompts generated by the telephone-based system. This study is one of the first to address adverse events in ambulatory patients outside the context of clinician visits and provides a model for addressing patient safety in chronic disease management.