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Introduction In this study, we investigate the effects of smoking on pain scores, vital signs, and analgesic consumption in the intraoperative and postoperative period in patients undergoing tympanomastoidectomy surgery. Methods A total of 100 patients with American Society of Anesthesiologists I-II status, aged 18–55 years, and who were planned to undergo tympanomastoidectomy surgery were divided into two groups: smokers (Group 1) and non-smokers (Group 2). The patients were compared for preoperative, intraoperative, and 24-hour postoperative carboxyhemoglobin, blood pressure, oxygen saturation, respiratory rate, heart rate, pain intensity and verbal numerical rating scales, the extent of patient-controlled tramadol dose, nausea, and vomiting. Results There were 50 individuals in each group. Postoperative analgesic consumption and pain scores were higher in Group 1, and the first postoperative pain was felt earlier. Furthermore, in Group 1, preoperative carboxyhemoglobin levels and postoperative nausea were statistically higher before, after, and at the tenth minute after induction, whereas oxygen saturation was lower. The two groups had no statistical difference regarding intraoperative and postoperative vital signs. Postoperative analgesic consumption was not affected by age or gender. Conclusions Smoking changes postoperative pain management, especially for this kind of operation, and these patients feel more pain and need more postoperative analgesic doses. Therefore, effective postoperative pain control should take account of smoking behavior, and analgesic doses may need to be adjusted for patients who smoke.