Resistance to antiemetic treatment with 5-hydroxytryptamine-3 receptor antagonist is an issue. This study evaluated the potential roles of ABCB1 and ABCG2 polymorphisms in antiemetic treatment resistance in patients with cancer previously enrolled in a randomized controlled trial. A total of 156 patients were evaluated for their responses to antiemetic therapy and then subdivided into granisetron or palonosetron groups. The genotypes were evaluated for their association with antiemetic efficacy in each treatment groups. Additional risk factors associated with complete response (CR) were examined using a multivariate regression analysis. No significant associations were identified for genetic polymorphisms in the palonosetron group. In the granisetron group, patients with ABCB1 2677TT and 3435TT genotypes had higher proportion of CR. In addition to ABCB1 polymorphisms, gender and cisplatin dose were associated with granisetron response by univariate analysis. Multivariate logistic regression analysis revealed that the ABCB1 3435C > T polymorphism and cisplatin dose were significant predictors of CR.