Background: The 5-hydroxytryptamine-3 antagonist antiemetics block the analgesic effect of tramadol. This prospective, randomized single-blinded study was designed to investigate the interaction between ramosetron and tramadol in females undergoing thyroidectomy. Method: We randomized 128 patients into two groups to receive ramosetron-tramadol (group R) or normal saline-tramadol (group N). Intravenous ramosetron (0.3 mg) or normal saline was administered at the induction of anesthesia, and 50 mg tramadol were given intravenously for postoperative analgesia 30 min before extubation. The analgesic regimen in the post-anesthesia care unit included additional 50 mg doses of tramadol if pain scores were >40 at rest. Postoperative pain was evaluated using an 11-point visual analog scale at 1 and 24 h postoperatively. Pain and nausea scores, analgesic and antiemetic doses, side effects, patient satisfaction with pain management, and postoperative nausea and vomiting were recorded 1 and 24 h after surgery. Results: The control group received 169.67 ± 46.80 mg tramadol vs. 168.33 ± 46.9 mg in the ramosetron group during the first 24 h after surgery (p=0.875). Total antiemetic dose was significantly lower in the ramosetron group than that in the control (p=0.012). Conclusions: We found that 0.3 mg ramosetron administered at the induction of anesthesia did not reduce the antinociceptive properties of tramadol.