The aim of this study was to evaluate whether aprepitant is an effective antiemetic when combined with 5-hydroxytryptamine 3-(5-HT3) receptor antagonists and dexamethasone in patients with breast cancer receiving anthracycline-based chemotherapy.A retrospective study was carried out on 229 patients with breast cancer between 2004 and 2014. All the patients received three cycles of cyclophosphamide, epirubicin and 5-fluorouracil. 5-HT3 receptor antagonists and dexamethasone were used in 132 patients (cohort 1). 5-HT3 receptor antagonists, dexamethasone and aprepitant were used in 97 patients (cohort 2). The primary outcome was to compare the grades of emesis between cohorts 1 and 2.The incidence of moderate and severe nausea was significantly lower in cohort 2 than in cohort 1 (p<0.05) during all three cycles. Additionally, the complete response rate (i.e. no nausea) was higher in cohort 2 (p<0.05).The combination of 5-HT3 receptor antagonists, dexamethasone and aprepitant was more effective as an antiemetic treatment than the standard dual combination of 5-HT3 receptor antagonists and dexamethasone for patients with breast cancer receiving anthracycline-based adjuvant chemotherapy.