Sugammadex produces recovery from neuromuscular blockade more rapidly and reliably than neostigmine. We sought to determine if sugammadex is associated with improved perioperative efficiency when compared to traditional neuromuscular blockade reversal with neostigmine, potentially offsetting the higher medication cost. This retrospective analysis involved patients receiving either neostigmine or sugammadex for reversal of neuromuscular blockade at a single academic tertiary care hospital. The final propensity-matched groups consisted of 4060 in each group (neostigmine or sugammadex). The primary outcome measured was total time in the operating room. Secondary outcomes included specific measures of perioperative efficiency as well as postoperative pulmonary failure. The average operating room time for patients was 169.59 [1.27] minutes for neostigmine and 157.06 [1.33] minutes for sugammadex (P < 0.001). The difference was primarily accounted for by shorter surgical times (121.45 [1.18] vs 109.62 [1.22] minutes, P < 0.011). Sugammadex was also associated with a shorter post-anesthesia care unit length of stay (102.47 [1.04] vs 98.67 [1.02] minutes, P < 0.001). For 8120 patients, sugammadex use was associated with shorter operating room and surgical durations as well as shorter post-anesthesia care unit stay. The favorable pharmacodynamic profile of sugammadex may improve surgical and perioperative efficiency and offset higher medication cost.