Background. We compared postoperative neuropsychological dysfunction after minimally invasive direct coronary artery bypass grafting (MIDCAB) operation with coronary artery bypass graft operations using cardiopulmonary bypass. Methods. Neuropsychological assessment was performed preoperatively and before discharge on 7 patients undergoing MIDCAB procedures, 9 patients undergoing single-graft cardiopulmonary bypass operation, and 27 patients undergoing multiple-graft cardiopulmonary bypass operation. From a matched control group of 40 normal subjects reliable change indices were derived for each measure and used to determine the incidence of postoperative decline. Results. There was little difference between the MIDCAB and single-graft cardiopulmonary bypass groups on the incidence of neuropsychologic decline. However, the multiple-graft cardiopulmonary bypass group had a significantly higher incidence of decline than the MIDCAB and single-graft cardiopulmonary bypass groups on specific neuropsychologic measures, coupled with a significantly greater number of postoperative deteriorations per patient. Conclusions. The elimination of cardiopulmonary bypass does not prevent neuropsychological dysfunction after cardiac operation as patients undergoing MIDCAB and single-graft cardiopulmonary bypass experience similar deteriorations in performance. However, the deterioration is markedly worsened when the number of surgical grafts is increased.