BACKGROUND: Capecitabine and oxaliplatin (XELOX) chemotherapy causes nausea and vomiting, despite adequate administration of antiemetics. Furthermore, specific risk factors that increase this risk are not elucidated. OBJECTIVE: To appraise the effectiveness of antiemetics to prevent XELOX-induced nausea and vomiting. METHODS: This was a single-center, prospective, cohort study. Patients were recruited on the day of chemotherapy and received follow-up after 5 days to assess nausea and vomiting and use of antiemetics. Patients were assessed for nausea and vomiting control and clinical endpoints of complete response, complete protection, and complete control. Multivariate logistic regression was used to evaluate the risk factors. RESULTS: Mean age of the 156 patients analyzed was 60 years (SD = 9.0) with 88 men (56.4%) and 68 women (43.6%). Patient proportions achieving complete response (87.8%), complete protection (80.8%), and complete control (62.8%) within 24 hours after chemotherapy declined throughout the follow-up period to 76.9%, 64.7%, and 48.7%, respectively. Patients with fewer than three risk factors (odds ratio [OR] = 3.13, p = .006), those receiving oxaliplatin less than 100 mg/m (OR = 3.23, p = .009) and capecitabine less than 1,500 mg/m (OR = 5.00, p = .04), were more likely to achieve complete response. CONCLUSIONS: An unacceptably high proportion of patients receiving XELOX were identified as being unable to attain adequate control of nausea because of inadequate usage of delayed antiemetic prophylaxis. Clinicians should be aware of the chemotherapy-induced nausea and vomiting patterns in this subgroup of patients on XELOX and tailor appropriate management plans. Incorporation of delayed antiemetics to existing institutional guidelines for chemotherapy-induced nausea and vomiting management may improve patients' tolerance of XELOX.