During robot-assisted radical cystectomy (RARC), specific surgical conditions (a steep Trendelenburg position, prolonged pneumoperitoneum, effective myoresolution until the final stages of surgery) can seriously impair the outcomes. The aim of the study was to evaluate the incidence of postoperative nausea and vomiting (PONV) and ileus and the quality of cognitive function at the awakening in two groups of patients undergoing different reversals. In this randomized trial, patients that were American Society of Anesthesiologists physical status (ASA) â‰¤III candidates for RARC for bladder cancer were randomized into two groups: In the sugammadex (S) group, patients received 2 mg/kg of sugammadex as reversal of neuromuscolar blockade; in the neostigmine (N) group, antagonization was obtained with neostigmine 0.04 mg/kg + atropine 0.02 mg/kg. PONV was evaluated at 30 min, 6 and 24 h after anesthesia. Postoperative cognitive functions and time to resumption of intestinal transit were also investigated. A total of 109 patients were analyzed (54 in the S group and 55 in the N group). The incidence of early PONV was lower in the S group but not statistically significant (S group 25.9% vs. N group 29%; p = 0.711). The Mini-Mental State test mean value was higher in the S group vs. the N group (1 h after surgery: 29.3 (29; 30) vs. 27.6 (27; 30), p = 0.007; 4 h after surgery: 29.5 (30; 30) vs. 28.4 (28; 30), p = 0.05). We did not observe a significant decrease of the PONV after sugammadex administration versus neostigmine use. The Mini-Mental State test mean value was greater in the S group.