Background: We evaluated the cognitive profile of 48 patients with major depression following their first myocardial infarction (MI). Methods: The cognitive performance of the patients was compared with the performance of 48 nondepressed MI patients and 48 healthy controls. Results: Depressed MI patients performed slower on a simple cognitive speed related measure compared with non-depressed MI patients and healthy controls. Attention and speed-related aspects of cognitive functioning were not affected. Surprisingly, (depressed) MI patients showed even better performances with respect to memory function. Limitation: No patients with non-MI-related depression were included. Conclusions: The cognitive profile of major depression after MI differs from that of non-cardiac-related depressive disorder, as described in the literature. This may reflect a different etiology of post MI depression from non-cardiac-related depression.