We aimed to compare the effects of ramosetron and palonosetron in the prevention of postoperative nausea and vomiting (PONV) in patients that received opioid-based intravenous patient-controlled analgesia (IV-PCA) after gynecological laparoscopy. We reviewed the electronic medical records of 755 adults. Patients were classified into two groups, ramosetron (group R, n=589) versus palonosetron (group P, n=166). Based on their confounding factors, 152 subjects in each group were selected after the implementation of propensity score matching. The overall incidence of PONV at postoperative day (POD) 0 was lower in group R compared to group P (26.9% versus 36.8%; P=0.043). The severity of nausea was lower in group R than in group P on postoperative day (POD) 0 (P=0.012). Also, the complete responder proportion of patients was significantly higher in group R compared to that in group P on POD 0 (P=0.043). In conclusion, ramosetron showed a greater efficacy in the prevention of postoperative nausea at POD 0 compared to palonosetron in patients after gynecological laparoscopy.