Thirty-eight healthy outpatients undergoing elective surgical procedures lasting 1–3 h were randomly assigned to receive either desflurane 3% (approximately 0.5 MAC) or isoflurane 0.6% (approximately 0.5 MAC) for maintenance of general anesthesia with nitrous oxide 60% in oxygen after a standardized induction sequence consisting of fentanyl 3 μ·kg−1, thiopental 4 μ·kg−1, and succinylcholine 1–1.5μ·kg−1, intravenously. Although anesthetic conditions were similar during operations in the two treatment groups, significant differences were noted in the recovery profiles as measured by elimination kinetics, psychometric testing, and visual analog scales (to assess subjective feelings). The time required for the end-tidal concentration to decrease by 50% was 2.5 ± 0.8 min for desflurane vs 9.5 ± 3.4 min for isoflurane (mean ± standard deviation [SD]). Times to awakening and ability to follow simple commands were significantly shorter after desflurane than after isoflurane (5.1 ± 2.4 vs 10.2 ± 7.7 min 6.5 ± 2.3 min vs 11.1 ± 7.9 min, respectively). Postoperatively, patients who received desflurane exhibited less impairment of cognitive function (as measured using the Digit-Symbol Substitution Test) than did those who received isoflurane. Furthermore, visual analog scores indicated that patients receiving desflurane experienced significantly less discomfort (pain), drowsiness, fatigue, clumsiness, and confusion in the early postoperative period. We conclude that desflurane may offer clinical advantages over isoflurane when used for maintenance of anesthesia during outpatient surgical procedures.