Objective To evaluate the feasibility and safety of fosaprepitant dimeglumine combined with palonosetron for the prevention and treatment of postoperative nausea and vomiting (PONV) after gynecologic laparoscopy. Metheods A total of 180 patients undergoing gynecological laparoscopic surgery were selected. According to the random number table method, they were divided into three groups (n=60): a palonosetron group (group A), a fosaprepitant dimeglumine group (group B), and a fosaprepitant dimeglumine combined with palonosetron group (group C). Group A received 0.075 mg palonosetron, group B was treated with 150 mg fosaprepitant dimeglumine, and group C received fosaprepitant dimeglumine 150 mg plus palonosetron 0.075 mg. Their PONV incidence at postoperative 2 h, on postoperative days 1 and 2, Visual Analogue Scale (VAS) scores on postoperative days 1 and 2, analgesia satisfaction scores, the number of PONV rescue cases (additional use of antiemetic agent metoclopramide/dexamethasone due to intolerance to vomiting) and the number of rescue analgesia cases within 2 d after surgery. The duration of operation, remifentanil dosage, the volume of blood loss, fluid intake, and the incidence of drug‑related adverse reactions were recorded. Results At postoperative 2 h, compared with group A, group C showed increases in the number of patients with grade 0 PONV, and decreases in the number of patients with grades 1, 2, and 3 PONV (all P<0.05). On postoperative days 1 and 2, compared with groups A and B, group C presented increases in the number of patients with grade 0 PONV, and decreases in the number of patients with grades 1, 2, and 3 PONV (all P<0.05). Compared with groups A and B, the satisfaction towards postoperative analgesia increased in group C (all P<0.05). There was no statistical difference in postoperative VAS scores among the three groups (all P>0.05). Furthermore, no statistical difference was found in the duration of operation, remifentanil dosage, the volume of blood loss, fluid intake, the number of PONV rescue cases and the number of rescue analgesia cases among the three groups (all P>0.05). No drug‑related adverse reactions occurred in the three groups. Conclusion The combined use of fosaprepitant dimeglumine and palonosetron is effective and safe to prevent PONV in patients undergoing laparoscopic gynecological surgery.