BackgroundEven though chemotherapy-induced nausea and vomiting (CINV) can be well controlled in the acute phase, the incidence of delayed CINV remains high. In this study, we intend to investigate whether prolonged use of NK-1 receptor antagonist (RA) in addition to 5-HT3 RA and dexamethasone (DEX) was more effective in preventing delayed CINV.MethodsThis randomised, open-label, controlled study was designed to compare the efficacy and safety of fosaprepitant 150 mg given on days 1,3 (prolonged group) versus on day 1 (regular group) in patients receiving highly emetogenic chemotherapy (HEC). All patients also treated with palonosetron on day 1 and DEX on days 1–3. The primary endpoint was the incidence of delayed nausea and vomiting. The second endpoint was AEs. All the above endpoints were defined according to CTCAE 5.0.ResultsSeventy-seven patients were randomly assigned to prolonged group and seventy-nine to regular group. Prolonged group demonstrated superiority in controlling delayed CINV to regular group, with statistically significant lower incidence of nausea (6.17% vs 12.66%,P= 0.0056), and slightly lower incidence of grade 1 vomiting (1.62% vs 3.80%,P= 0.0953) in the delayed phase. In addition, prolonged use of fosaprepitant was safe. No significant difference was found between the two groups regarding constipation, diarrhea, hiccough, fatigue, palpitation and headache in delayed phase.ConclusionsProlonged use of fosaprepitant can effectively and safely prevent delayed CINV in patients receiving HEC.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12885-023-11070-3.