Objective To explore the appropriate anesthetic method of percutaneous left atrial appendage closure by comparing the safety and feasibility of the different anesthetic methods. Methods Ninety nine patients with percutaneous left atrial appendage closure were divided into three groups according to anesthetic scheme by using a method of Historical Cohort Research: laryngeal mask general anesthesia without muscle relaxant (L group, n=19), endotracheal intubation general anesthesia with muscle relaxation antagonist (S group, n=40), and endotracheal intubation general anesthesia without muscle relaxation antagonist (G group, n=40). Target controlled infusion(TCI) of propofol and remifentanil for anesthesia induction and maintenance were used in L group and S group. The laryngeal mask was used in L group without muscle relaxants. Rocuronium was used for endotracheal intubation in S group，but the muscle relaxation was antagonized by sugammadex at the end of operation. Endotracheal intubation was performed after TCI propofol, intravenous sufentanil and cisatracurium in G group, but the muscle relaxation was not antagonized at the end of the operation. The outcome indexes were as follows: the time of spontaneous respiration, the time of consciousness recovery, the time of extubation, the time of staying at the postanesthesia care unit (PACU), the successful rate of esophageal ultrasonic probe placement, the incidence of displacement and air leakage of laryngeal mask, the incidence of replacement of a laryngeal mask with tracheal intubation during operation, and the adverse events after awakening. Results The recovery time of autonomic respiration in S group and L group were significantly shorter than that in G group ［(2.5±0.5), (1.9±0.6) min vs (22.2±7.1) min, P<0.05］. The recovery time of consciousness was (3.4±0.6), (2.7±0.6) min in L group and S group respectively, both which were significantly shorter than that in G group ［(28.8±12.9) min, P<0.05］. The time of extubation in L and S group was (4.5±1.0), (3.6±1.0) min respectively, both which were significantly shorter than that in G group ［(34.6± 16.0) min, P<0.05]. The time of staying at PACU in L group and S group was (28±4), (26±5) min respectively, which were significantly shorter than that in G group［(65±20) min, P<0.05］. The successful rate of one-time placement of TEE was 42.1% in L group, but that in S group and G group was more than 95% respectively(P<0.05). The intraoperative displacement rate in L group was 36.8%. The incidence of replacement of a laryngeal mask with tracheal intubation during operation was 21.1% in L group(P<0.05). The incidence of transient hypoxemia, agitation, nausea and vomiting and urinary retention were lower in S group and L group than in G group after awakening(P<0.05). Conclusions Endotracheal intubation general anesthesia was performed by combined intravenous injection of rocuronium with TCI propofol and remifentanil and reversal of rocuronium by sugammadex, which have the advantages of safe airway controllability, recovery rapidly after operation, extubation earlier, the lower incidence of hypoxemia and the lower incidence of agitation. Therefore, this anesthetic pattern is an ideal anesthetic method for percutaneous left atrial appendage closure.