OBJECTIVES: To determine the cost-effectiveness of the risk model-guided (RMG) compared with physician’s choice (PC) antiemetic prophylaxis in patients receiving chemotherapy for early-stage breast cancer. METHODS: We conducted a cost-utility analysis based on a published randomized controlled trial of 324 patients with early stage breast cancer undergoing chemotherapy for the first time at two cancer care centers in Ottawa, Ontario, Canada. Patients were randomized to either the RMG or the PC arm. Patients in the RMG arm had their antiemetic risk scores calculated before each cycle of pharmacotherapy, and their antiemetic treatments were adjusted based on their risk scores. Patients in the PC group received antiemetic drugs according to the treating physician’s preference. The effectiveness was expressed as quality-adjusted life year (QALY). Cost and utility data were obtained from the Canadian published literature. We used generalized estimating equations to estimate the incremental net benefits and their 95% CIs over the range of willingness-to-pay values from the Canada’s healthcare system and societal perspectives. Based on the same regression approach, we calculated incremental cost-effectiveness ratios and with 95% CIs. A series of sensitivity analyzes will be conducted. RESULTS: The trial included 324 patients. Significantly fewer patients in the RMG group experienced acute and delayed nausea/vomiting than those in the PC group.  The incremental net benefit was positive over the range of willingness-to-pay values for both healthcare system and societal perspectives, suggesting that the RMG was a cost-effective intervention. Results of the cost-effectiveness acceptability curve indicated that the probability of the RMG is cost-effective increased with a greater value of willingness-to-pay. The results of sub-group analyses by the history of motion or morning sickness and chemotherapy cycles will be presented. CONCLUSIONS: The risk model-guided antiemetic prophylaxis is an economically attractive option compared with antiemetic prophylaxis by physician’s preference in patients receiving chemotherapy for early-stage breast cancer.