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In Japan, routine clinical care does not normally involve the use of a monitoring device to guide the administration of neuromuscular blocking drugs or their antagonists. Although most previous reports demonstrate that sugammadex offers more rapid and reliable antagonism from rocuronium-induced neuromuscular blockade, this advantage has not been confirmed in clinical settings when no neuromuscular monitoring is used. In this multicenter observational study, we sought to determine whether sugammadex reduces the incidence of postoperative residual weakness compared with neostigmine when the administration of rocuronium and its antagonists is not guided by neuromuscular monitoring.This study was conducted in two 5-month periods that preceded and followed the introduction of sugammadex into clinical practice in Japan. Five university-affiliated teaching hospitals participated in this study. Neostigmine was used to antagonize rocuronium-induced neuromuscular blockade in the first phase, and sugammadex was used in the second phase. The timing and doses of rocuronium, neostigmine, and sugammadex were determined by the attending anesthesiologists without the use of neuromuscular function monitoring devices. To ascertain the incidence of postoperative residual neuromuscular weakness, the train-of-four ratio (TOFR) was determined acceleromyographically after tracheal extubation. Since our practice also does not usually involve calibration and normalization of accelerographic responses, both TOFR <0.9 and TOFR <1.0 were used as the criteria for defining postoperative residual weakness.In the first phase, 109 patients received neostigmine (average dose 33 µg/kg) and 23 patients were considered (by clinical criteria) to have adequate recovery and did not receive neostigmine (spontaneous recovery group). In the second phase, 117 patients received sugammadex (average dose 2.7 mg/kg) for antagonism of rocuronium-induced blockade. The incidence (95% confidence interval) of TOFR <0.9 under spontaneous recovery, after neostigmine, and after sugammadex, was 13.0% (2.8%–33.6%), 23.9% (16.2%–33.0%), and 4.3% (1.7%–9.4%), respectively. The incidence (95% confidence interval) of TOFR <1.0 in these groups was 69.6% (47.1%–86.6%), 67.0% (57.3%–75.7%), and 46.2% (36.9%–55.6%), respectively. The use of sevoflurane in the neostigmine group and the short interval between the administration of the last doses of rocuronium and sugammadex were associated with a higher incidence of postoperative residual weakness.This study demonstrated that the risk of TOFR <0.9 after tracheal extubation after sugammadex remains as high as 9.4% in a clinical setting in which neuromuscular monitoring (objective or subjective) was not used. Our finding underscores the importance of neuromuscular monitoring even when sugammadex is used for antagonism of rocuronium-induced neuromuscular block.