Purpose We assessed the efficacy of palonosetron (PAL) in comparison to granisetron (GRA) for the treatment of CINV using the self-assessment questionnaires. In addition, we analyzed the serum levels of emetic various biomarkers. Methods We conducted a randomized study of 70 patients naïve to chemotherapy. The primary endpoint was the late phase score on the MAT questionnaire. The plasma concentrations of the biomarkers were measured on days 1 and 3. Results There were no statistical differences in the scores on the questionnaires, but the mean values in response to PAL were higher than those in response to GRA. The value of ghrelin on day 1 was significantly higher for GRA than for PAL. Conclusions For the primary endpoint, the score of the late phase on the MAT questionnaire was not statistically different between the PAL and GRA treatment groups. Further studies are needed to clarify the role of ghrelin for the treatment of CINV.