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There is controversy regarding the relative perioperative benefits of desflurane versus sevoflurane when used for maintenance of anesthesia in the ambulatory setting. Although studies have consistently demonstrated a faster emergence with desflurane (versus sevoflurane), the impact of this difference on the later recovery end points has not been definitively established. Furthermore, the effect of desflurane (versus sevoflurane) on the incidence of coughing is also controversial.We randomized 130 outpatients undergoing superficial surgical procedures requiring general anesthesia to one of two maintenance anesthetic treatment groups. All patients were induced with propofol, 2 mg/kg IV, and after placement of a laryngeal mask airway, anesthesia was maintained with either sevoflurane 1%–3% or desflurane 3%–8% in an air/oxygen mixture. The inspired concentration of the volatile anesthetic was varied to maintain hemodynamic stability and a Bispectral Index value of 50–60. Analgesia was provided with local anesthetic infiltration and ketorolac (30 mg IV). Antiemetic prophylaxis consisted of a combination of ondansetron (4 mg), dexamethasone (4 mg), and metoclopramide (10 mg) at the end of surgery. Assessments included recovery times to eye opening, response to commands, orientation, fast-track score of 14, first oral intake, sitting, standing, ambulating unassisted, and actual discharge. Patient satisfaction with anesthesia, the ability to resume normal activities on the first postoperative day, adverse side effects (e.g., coughing, purposeful movement, oxygen desaturation <90%, sore throat, postoperative nausea, and vomiting), and the requirement for postoperative analgesic and antiemetic drugs were recorded in the early postoperative period and during the initial 24-h period after discharge.The two study groups had comparable demographic characteristics. Although the overall incidence of coughing during the perioperative period was higher in the desflurane group (60% versus 32% in the sevoflurane group, P < 0.05), the incidences of coughing during the actual administration of the volatile anesthetics (i.e., the maintenance period) did not differ between the two groups. Emergence from anesthesia was more rapid after desflurane; however, all patients achieved fast-track recovery criteria (fast-track score ≥12) before leaving the operating room. Finally, the time to discharge home (90 ± 31 min in sevoflurane and 98 ± 35 min in desflurane, respectively) and the percentage of patients able to resume normal activities on the first postoperative day (sevoflurane 48% and desflurane 60%) did not differ significantly between the two anesthetic groups.Use of desflurane for maintenance of anesthesia was associated with a faster emergence and a higher incidence of coughing. Despite the faster initial recovery with desflurane, no significant differences were found between the two volatile anesthetics in the later recovery period. Both volatile anesthetics should be available for ambulatory anesthesia.