Seventy multi-infarct dementia patients were randomized into an aspirin-treated group and an untreated control group for an exploratory investigation to determine any effects of 325 mg aspirin daily on cognitive performance. The control group did not receive placebo but evaluations were carried out in a blinded manner. The index group (N = 37, mean age 67.1 years) received 325 mg of aspirin by mouth once daily while the control group (N = 33, mean age 67.6 years) was followed and treated in a similar manner except that they received no aspirin. Both groups had comparable risk factors for stroke, which were treated similarly, as well as comparable initial cerebral blood flow values, as measured by the 133xenon inhalation method, and initial scores on Cognitive Capacity Screening Examination testing. Patients were evaluated at intervals of one year. Significant improvements were demonstrated for cerebral perfusion values (P less than .0001) and cognitive performance scores (P less than .0001) among aspirin-treated patients compared to untreated controls at each of three annual follow-up evaluations. Both men and women benefited from aspirin therapy and their quality of life and independence appeared to be improved, which was not apparent in the control group. Daily aspirin appears to improve or stabilize declines in cerebral perfusion and cognition among patients with multi-infarct dementia.