Background Palonosetron is a serotonin-3 (5-HT3) receptor antagonist indicated in the prevention of chemotherapy-induced nausea and vomiting (CINV) in pediatric and adult patients. Traditional dosing for palonosetron in the pediatric population has been 20 mcg/kg with a maximum dose of 1500 mcg. This study aimed to evaluate the impact of an institutional dose cap of 750 mcg on pediatric CINV. Procedure This is a retrospective chart review of admitted patients given palonosetron intended for prevention of CINV at a pediatric medical center between July 1, 2018 and June 30, 2020. Patients 1 month up to 17 years of age who received at least one dose of palonosetron prior to chemotherapy (not preceding stem cell transplant) were included. Information regarding chemotherapy, antiemetic premedication, emesis, and breakthrough antiemetic agents were recorded to quantify the instances of CINV. Results Seven hundred and seventy-one patient encounters met inclusion criteria (n=485 traditional dose, n=286 dose capped). There was no statistical difference in the instances of emesis (p=0.98) or breakthrough agents administered (p=0.65) between the two groups. Dose capping patients at 750 mcg reduced cost by approximately 34.9% compared to traditional dosing. Conclusions The use of a dose cap of palonosetron at 750 mcg maintains efficacy for prevention of CINV while reducing cost in pediatric patients receiving chemotherapy.