Background Endotracheal extubation under deep anesthesia (deep extubation) has been proved to present stable hemodynamics and steady intracranial pressure during emergence from anesthesia in patients undergoing craniotomy. This study aims to examine, in comparison with deep extubation, if a laryngeal mask airway (LMA) could provide a safer and smoother emergence from anesthesia in patients undergoing craniotomy. Methods This prospective randomized controlled study was conducted on patients undergoing elective craniotomy for brain tumors. After the complement of the surgical procedure, the patients had anesthesia maintained with end-tidal sevoflurane concentration 2.5% and also fully regained muscle power (Time Zero), they were randomly assigned to ETT Group (n = 29) for deep extubation or to LMA Group (n = 29), where the endotracheal tube was replaced by a laryngeal mask airway. The primary outcomes were respiratory complications, airway interventions and hemodynamic changes through emergence from anesthesia till 30 min following Time Zero. The secondary outcomes were re-operation incidence in 24 h, stay time in the intensive care unit and postoperative hospital days. Results At 5 min before Time Zero either oxygen partial pressures (PaO2) or carbon dioxide partial pressures (PaCO2) between the two groups were comparable. No significant PaCO2 change was noted in both groups in 5 min after Time Zero, yet there was a remarkably lower PaO2 in ETT Group at that time point, 188.9 (± 71.1) in ETT Group vs 264.4 (± 85.4) in LMA Group. In ETT Group, coughs and snores were considerably more frequent, and thus more interventions were needed to maintain adequate respiration. From Time Zero on, blood pressures (systolic, diastolic and mean) and heart rates in ETT Group were generally higher than those in LMA Group, but the differences were insignificant at all time points except heart rate at 10 min after Time Zero. The secondary outcomes between the two groups were similar. Conclusions Compared with deep extubation, a LMA, as a temporary airway replacement, facilitates a safer and smoother emergence from anesthesia for patients undergoing craniotomy, in terms of better oxygen saturation, fewer respiratory complications and fewer airway interventions. Trial registration The study was conducted after receiving approval from Institutional Review Board of Chang Gung Memorial Hospital, Linkou Branch, Taiwan (registration number 202102115A3; January 27, 2022), and the clinicaltrials.gov (NCT05253404) on 23 February 2022.