Objective To compare the effects of neurokinin-1 (NK-1) receptor antagonist (RA) plus tropisetron versus dexamethasone plus tropisetron against moderately emetogenic chemotherapy-induced nausea and vomiting (MECCINV). Methods A non-inferiority trial was designed. Patients who received moderately emetogenic chemotherapy in Department of Oncology of General Hospital of Southern Theater Command of PLA from Apr. 2021 to Jan. 2022 were randomly assigned to NK-1 RA (NK-1 RA+tropisetron) group or dexamethasone (tropisetron+dexamethasone) group by random number table method. Primary evaluation indexes were complete response (CR) rates of vomiting at overall phase (0- 120 h), delayed phase (24-120 h) and acute phase (<24 h). Secondary evaluation indexes were complete control (CC) rate of nausea and total response (TR) rate of nausea and vomiting at each phase. Safety indexes were adverse events (symptoms such as fatigue, constipation, hiccup and insomnia; abnormal laboratory indicators such as decline of leukocyte, neutrophil, hemoglobin and platelet and increase of alanine transaminase and/or aspartate transaminase and serum creatinine). The intervention effects of the 2 groups were compared by difference test (test level was 0.05) and non-inferiority test (noninferiority margin was 15 %, and test level was 0.025). Results A total of 101 patients participated in the study, including 51 in the NK-1 RA group and 50 in the dexamethasone group. The CR rates of vomiting at overall phase in the NK-1 RA group and dexamethasone group were 58.8 % (30/51) and 56.0 % (28/50), respectively, and non-inferiority test showed no statistical significance (P_{non-inferiority}=0.035, rate difference[RD]=2.80 %, 95 % confidence interval[CI]-16.5 %-22.1 %); the CR rates of vomiting at acute phase were 80.4 % (41/51) and 78.0 % (39/50), respectively, and non-inferiority test was statistically significant (P_{non-inferiority}=0.016, RD=2.40 %, 95 % CI -13.4 %-18.2 %); and the CR rates of vomiting at delayed phase were 62.7 % (32/51) and 58.0 % (29/50), respectively, and non-inferiority test was statistically significant (P_{non-inferiority}=0.021, RD=4.70 %, 95 % CI -14.4 %-23.8 %). The CC rate of nausea at each phase was slightly higher in the NK-1 RA group than that in the dexamethasone group, and the non-inferiority test was statistically significant (all P_{non-inferiority}<0.025). There was no significant difference in the safety indicators between the 2 groups (all P>0.05). Conclusion In MEC-CINV patients, the control effect of antiemetic regimen of NK-1 RA combined with tropisetron on nausea and vomiting is non-inferior to the standard dual regimen dexamethasone combined with tropisetron, and the safety is good.