This study compared the efficacy of three-drug antiemetic regimens (olanzapine, fosaprepitant, and 5-HT3 receptor antagonist versus dexamethasone, fosaprepitant, and 5-HT3 receptor antagonist) on chemotherapy-induced nausea and vomiting (CINV) in children. Complete response (CR) was defined as no emesis or use of rescue antiemetics. In the acute phase, 52% of patients in the olanzapine group achieved a CR compared to 63% in the dexamethasone group (p=0.354). In the delayed phase, CR was 80% versus 73% (p= 0.702), respectively. Olanzapine is an acceptable agent to use in place of dexamethasone when a patient is not a candidate for corticosteroid as CINV prophylaxis.