Sugammadex has several pharmacological advantages over neostigmine, including faster reversal of neuromuscular blockade and fewer adverse effects. However, the economic impact of sugammadex remains controversial due to the considerable heterogeneity of study designs and clinical settings in previous studies. In a post-hoc analysis of a randomized controlled trial, we evaluated patients who underwent elective surgeries and general anesthesia with endotracheal intubation in a medical center in Taiwan between March 2020 and August 2020. Patients were divided into either the sugammadex or neostigmine group based on the neuromuscular blocking drug used. Propensity score matching was used to balance the baseline patient characteristics between the two groups. The patient’s recovery from anesthesia and the putative cost-effectiveness of sugammadex versus neostigmine was assessed. Derived cost-effectiveness using personnel costs in the operating room and the post-anesthesia care unit was estimated using multiple linear regression models. A total of 2587 and 1784 patients were included before and after matching, respectively. Time to endotracheal extubation was significantly shorter in the sugammadex group (mean 6.0 ± standard deviation 5.3 min) compared with the neostigmine group (6.6 ± 6.3 min; p = 0.0032). In addition, the incidence of bradycardia was significantly lower in the sugammadex group (10.2%) compared with the neostigmine group (16.9%; p < 0.001). However, the total costs were significantly lower in the neostigmine group (50.6 ± 21.4 United States dollars) compared with the sugammadex group (212.0 ± 49.5 United States dollars). Despite improving postoperative recovery, the benefits of sugammadex did not outweigh its higher costs compared with neostigmine, possibly due to the low costs of labor in Taiwan’s healthcare system.