Postoperative nausea and vomiting (PONV) is an important clinical problem. Aprepitant is a relatively new agent for this condition which may be superior to other treatment. A systematic review was performed after searching a number of medical databases for controlled trials comparing aprepitant with conventional antiemetics published up to 25 April 2015 using the following keywords: ‘Aprepitant for PONV’, ‘Aprepitant versus 5-HT3 antagonists’ and ‘NK-1 versus 5-HT3 for PONV’. The primary outcome for the pooled analysis was efficacy of aprepitant in preventing vomiting on postoperative day (POD) 1 and 2. 172 potentially relevant papers were identified of which 23 had suitable data. For the primary outcome, 14 papers had relevant data. On POD1, 227/2341 patients (9.7%) patients randomised to aprepitant had a vomiting episode compared with 496/2267 (21.9%) controls. On POD2, the rate of vomiting among patients receiving aprepitant was 6.8% compared with 12.8% for controls. The OR for vomiting compared with controls was 0.48 (95% CI 0.34 to 0.67) on POD1 and 0.54 (95% CI 0.40 to 0.72) on POD2. Aprepitant also demonstrated a better profile with a lower need for rescue antiemetic and a higher complete response. Efficacy for vomiting prevention was demonstrated for 40 mg, 80 mg and 125 mg without major adverse effects. For vomiting comparison there was significant unexplainable heterogeneity (67.9% and 71.5% for POD1 and POD2, respectively). We conclude that (1) aprepitant reduces the incidence of vomiting on both POD1 and POD2, but there is an unexplained heterogeneity which lowers the strength of the evidence; (2) complete freedom from PONV on POD1 is highest for aprepitant with minimum need for rescue; and (3) oral aprepitant (80 mg) provides an effective and safe sustained antivomiting effect.