Postoperative cognitive dysfunction (POCD) increases morbidity and mortality. The mechanisms underlying POCD remain elusive; however, systemic responses induced by anesthesia and surgery might trigger neuroinflammation and POCD. Desflurane is a preferable volatile anesthetic agent for elderly patients because it facilitates shorter recovery from general anesthesia. The aim of this study was to determine whether quality of emergence and cognitive function in elderly patients undergoing a long duration desflurane anesthesia are better than those in the case of sevoflurane anesthesia. Forty-two patients who were older than 65 years of age and scheduled for surgery of more than 4 h in duration were enrolled in this study. Patients were randomly assigned to a desflurane anesthesia group (D group) and sevoflurane anesthesia group (S group). General anesthesia was maintained with 3.5 % desflurane (D group) and 1.0 % sevoflurane (S group). The Mini-Mental State Examination (MMSE) was used for assessing cognitive function 24 h before and after surgery. Postoperative MMSE score in the D group was significantly improved compared to that in the preoperative period. In conclusion, elderly patients undergoing desflurane anesthesia have significantly better quality of emergence and may have better cognitive function than those in elderly patients undergoing sevoflurane anesthesia.