BACKGROUNDAvoidance of airway complications and rapid emergence from anaesthesia are indispensable for the use of a laryngeal mask airway (LMA). Evidence from adequately powered randomised studies with a low risk of bias for the optimal anaesthetic in this context is limited.OBJECTIVEWe tested the hypothesis that when using remifentanil-based intra-operative analgesia, desflurane would be the most suitable anaesthetic: with noninferiority in the occurrence of upper airway complications and superiority in emergence times compared with sevoflurane or propofol.DESIGNA randomised, multicentre, partially double-blinded, three-arm, parallel-group study.SETTINGTwo university and two regional German hospitals, from February to October 2015.PATIENTSA total of 352 patients (age 18 to 75 years, ASA physical status I to III, BMI less than 35 kg m−2 and fluent in German) were enrolled in this study. All surgery was elective with a duration of 0.5 to 2 h, and general anaesthesia with a LMA was feasible.INTERVENTIONThe patients were randomised to receive desflurane, sevoflurane or propofol anaesthesia.MAIN OUTCOME MEASURESThis study was powered for the primary outcome ‘time to state date of birth’ and the secondary outcome ‘intra-operative cough’. Time to emergence from anaesthesia and the incidence of upper airway complications were assessed on the day of surgery.RESULTSThe primary outcome was analysed for 343 patients: desflurane (n=114), sevoflurane (n=111) and propofol (n=118). The desflurane group had the fastest emergence. The mean (± SD) times to state the date of birth following desflurane, sevoflurane and propofol were 8.1 ± 3.6, 10.1 ± 4.0 and 9.8 ± 5.1 min, respectively (P < 0.01). There was no difference in upper airway complications (cough and laryngospasm) across the groups, but these complications were less frequent than in previous studies.CONCLUSIONWhen using a remifentanil infusion for intra-operative analgesia in association with a LMA, desflurane was associated with a significantly faster emergence and noninferiority in the incidence of intra-operative cough than either sevoflurane or Propofol.TRIAL REGISTRATIONClinicalTrials.gov identifier: NCT02322502; EudraCT identifier: 2014-003810-96.