OBJECTIVE To compare the effects of propofol versus sevoflurane on the outcomes of patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). METHODS A total of 110 patients undergoing cardiac surgery with CPB in our hospital from January 2015 to June 2017 were randomly divided into 2 groups (n=55): Group A, in which anesthesia was maintained with sevoflurane, and Group B, in which anesthesia was maintained with propofol. The MMSE score before and after operation, perioperative laboratory index, incidence of postoperative cognitive dysfunction (POCD) and incidence of adverse events between the two groups were compared. RESULTS The MMSE score was significantly higher in Group B than in Group A after anesthesia (p<0.05). Serum levels of the brain injury markers neuron-specific enolase, S100β and matrix metalloproteinase 9 were significantly lower in Group B than in Group A (p<0.05). POCD incidence at 12 hour and 24 hour after operation was significantly lower in Group B than in Group A (p<0.05). There were no significant differences in the incidence of low cardiac output and thoracotomy bleeding between two groups. CONCLUSIONS Compared with sevoflurane, the use of propofol during cardiac surgery with CPB can efficiently improve postoperative cognitive function without increasing the risk of adverse reactions.