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Remifentanil and nitrous oxide (N2O) are 2 commonly used anesthetic agents. Both these agents are known risk factors for postoperative nausea and vomiting (PONV). However, remifentanil and N2O have not been directly compared in a published study. Remifentanil can induce acute tolerance or hyperalgesia, thus affecting postoperative pain. The objective of this retrospective study is to compare the effects of remifentanil and N2O on PONV and pain in patients receiving intravenous patient-controlled analgesia (IV-PCA) after thyroidectomy.We analyzed the electronic medical records of 992 patients receiving fentanyl-based IV-PCA after thyroidectomy at Chung-Ang University Hospital from January 1, 2010 to April 30, 2016. We categorized the patients according to anesthetic agents used: group N2O (n = 745) and group remifentanil (n = 247). The propensity score matching method was used to match patients in the 2 groups based on their covariates. Finally, 128 matched subjects were selected from each group.There were no differences between groups for all covariates after propensity score matching. The numeric rating scale for nausea (0.55 ± 0.88 vs 0.27 ± 0.76, P = 0.01) was higher and complete response (88 [68.8%] vs 106 [82.8%], P = 0.001) was lower in group N2O compared with group remifentanil on postoperative day 0. However, the visual analog scale score for pain (3.47 ± 2.02 vs 3.97 ± 1.48, P = 0.025) was higher in group remifentanil than group N2O on postoperative day 0.In patients receiving IV-PCA after thyroidectomy, postoperative nausea was lower but postoperative pain was higher in group remifentanil.