Abstract Aim. To compare the effectiveness of fosaprepitant and droperidol as addition to standard prevention of postoperative nausea and vomiting (PONV) after subtentorial craniotomy. Material and methods. A randomized prospective study included 40 patients. All patients underwent the same type of anesthesia. Fosaprepitant 150 mg was administered as intravenous infusion over 20 min in the first group (n=20) immediately after induction of anesthesia. In the second group (n=20), droperidol 1.25 mg (0.5 ml) was intravenously injected at the end of surgery. All patients underwent standard pharmacological prophylaxis with dexamethasone and ondansetron. The data were aggregated by a survey within 48 hours after surgery in patients who underwent elective interventions at the Burdenko Center for Neurosurgery in April — August 2018. Results. Both groups were comparable by demographic and clinical data. Overall incidence of PONV in group 1 was 20% (4 out of 20), in group 2 — 55% (11 out of 20 patients) (RR 0.4, 95% CI 0.14—0.95; p<0.05). Incidence of PONV within 12 hours after tracheal extubation was 10% in group 1 (2 patients) and 40% in group 2 (8) (RR 0.3, 95% CI 0.06—1.03, p<0.05). Fosaprepitant almost completely prevented postoperative vomiting (5% in group 1 vs. 45% in group 2; p<0.05). In both groups, symptoms of nausea and vomiting were common within 8—24 hours after surgery as a rule. Conclusion. Administration of fosaprepitant as a supplement to standard prevention of PONV is more effective compared with droperidol in patients undergoing subtentorial craniotomy. Neurokinin receptor antagonists may be perspective drugs for prevention of postoperative emetogenic reactions. However, further researches are necessary.