BACKGROUND: The ability of patients to perform day-to-day tasks (e.g., medication management, dietary regulation) is an important concern of transplant teams. METHODS: We studied a clinical series of 75 heart transplant candidates and 38 controls to examine the predictive validity of demographic, neuropsychologic, and cardiac function variables to a performance-based measure of instrumental activities of daily living (IADL) capacity (i.e., Everyday Problems Test, EPT). RESULTS: Multiple regression analyses, controlling for education and race, indicated that neuropsychologic tests accounted for between 34% and 67% of the variance across IADL domains (e.g., cooking, household chores, medication management). The IADL capacity was most consistently predicted by long-standing verbal ability (Shipley Institute of Living Scale-Vocabulary, SILS-VOC) and psychomotor speed and mental flexibility (Trail Making Test-Part B, TMT-B). Similarly, SILS-VOC and TMT-B also tended to show the best operating characteristics (i.e., sensitivity, specificity, positive predictive power, negative predictive power) for detection of dependence across IADL domains. In contrast, cardiac function measures (e.g., cardiac output, mean atrial pressure) were largely unrelated to the patient's performance on the paper-and-pencil EPT task. CONCLUSIONS: Long-standing intellectual ability, and a measure of speeded information processing and mental flexibility are the best predictors of IADL capacity.