Background: Nausea and vomiting are common complications on the chemotherapy (CINV) and can affect the quality of life of the patients. There are various antiemetic regiments that varies in both cost and effectiveness. The aim of this trial is to evaluate the efficacy in acute and delayed CINV of ondansetron vs palonosetron. Patients and methods: In his was a randomized, open label trial, we included breast cancer patients' candidate to (AC, TC, TCH regimens); arm A received palonosetron, dexamethasone and fosaprepitant and arm B ondansetron, dexamethasone, fosaprepitant; patients who had received previously any chemotherapy or radiotherapy were excluded.Presence of CINV were investigated, as well the ER visits due for CINV and QoL (EORTC QLQ 30 and EORTC B-23) were analyzed during the first cycle of treatment. Local ethics committee approved the trial. Results: 262 patients were included, 87% received AC and 13% TC; acute control was achieved in 87% and 94% respectively, p=ns and delayed control was achieved in 76% and 86% p=ns, toxicity was similar in both arms. QoL analysis showed no differences in family interaction, social life and financial troubles. ER visits due to severe symptoms were similar p=ns Conclusions: Palonosetron or ondansetron are equally effective in prevention acute and delayed CINV and they also maintain similar quality of life. Citation Format: Arce-Salinas C, Deneken-Hernandez Z, Flores-Diaz D, Gonzalez-Serrano JP, Matus-Santos JA, Ruiz-Garcia E, Calderillo-Ruiz G, Macedo O, Santamaría-Galicia J, Aguilar-Ponce JL, Reynoso-Noverón N. Efficacy and quality of life analysis of palonosetron vs ondansetron for high and moderate emetogenic chemotherapy for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-14.