Antiplatelet substances, generally aspirin, have become widely used for secondary prevention of ischemic heart disease. Used in relatively small doses, it is generally assumed that aspirin has no psychoactive effect. The present study took advantage of a sample of 174 males undergoing coronary angiography to see if regular aspirin use as prophylactic therapy for ischemic heart disease was associated with one or more of a number of measures of emotional distress. Aspirin use was found to be associated with less depression and anxiety or worry, as reported by the patient and as perceived by a significant other. Despite a significant association of aspirin use with the presence of documented coronary artery disease, the association of aspirin use and diminished distress could not be accounted for by the previously observed high prevalence of depressed/anxious individuals among patients with negative or nominal results on angiography, or by a number of other demographic or clinical variables such as age and socioeconomic status. Although only correlational in nature, present results raise the question of whether aspirin may have a beneficial mood-modulating effect.