The purpose of this study was to explore how patients use narratives to create coherent understandings of risks associated with complex antithrombotic therapies. We led four focus groups consisting of patients older than 65 years of age who had a diagnosis of cardiovascular disease and were using a prescription for cardioprotective agents, such as aspirin, anticoagulants, and/or antiplatelets. The participants' stories were retrospective accounts about physician and patient interactions and adverse events organized in the plot structure of a trial-and-error story. The trial-and-error narrative structure emphasizes patients' idiosyncrasies and reasons why they expect to experience adverse events from changes in treatment. Any fears that they might have had about these risks were mitigated by physician expertise, patient responsibility, and medical technology. Patients who expressed concern about not having sufficient access to medical expertise (e.g., physicians, laboratory tests) seemed less willing to accept risks. The trial-and-error risk narratives helped patients deal with ambiguity and uncertainty about the outcomes of their therapies, and revealed patients' orientations to the risks they faced.