We aim to compare the effects of sugammadex on postoperative nausea and vomiting (PONV) with those of neostigmine–atropine mixture. A total of 136 American Society of Anesthesiology (ASA) I or II patients, aged 18 to 65 years who underwent ear, nose, and throat (ENT) surgery under general anesthesia, were recruited in this prospective, randomized, double-blind study to receive either sugammadex 2 mg/kg or neostigmine 2.5 mg with atropine 1 mg for reversal of neuromuscular blockade. PONV scores and the need for the rescue of anti-emetic were assessed upon arrival in the post-anesthesia recovery unit and at 1-, 6-, 12-, and 24-h post-reversal. The incidence of PONV was significantly lower in patients who received sugammadex (3%) compared to patients who received neostigmine–atropine mixture (20%) at 6 h postoperative (p = 0.013). The incidence of PONV was comparable at other time intervals. None of the sugammadex recipients require rescue antiemetic whereas two patients from the neostigmine–atropine group required rescue antiemetic at 1 and 6 h post-reversal, respectively. The need for the rescue antiemetic was not statistically significant. We concluded that reversal of neuromuscular blockade with sugammadex showed lower incidence of PONV compared to neostigmine–atropine combination in the first 6 h post-reversal.