Purpose: To update the 2009 recommendations for the prevention of acute chemotherapy-induced emesis in children. Methods: We updated the original systematic literature search. Randomized studies were included in the evidence to support this guideline if they were primary studies fully published in full text in English or French; included only children less than 18 years old or, for mixed studies of adults and children, reported the pediatric results separately or the median or mean age was no more than 13 years; evaluated acute chemotherapy-induced nausea and vomiting (CINV) prophylaxis; provided sufficient information to permit determination of the emetogenicity of the antineoplastic therapy administered or the study investigators stated the emetogenicity of the chemotherapy administered; included an implicit or explicit definition of complete acute CINV response; described the antiemetic regimen in full; and reported the complete acute CINV response rate as a proportion. Results: Twenty-five randomized studies, including eight published since 2009, met the criteria for inclusion in this systematic review. Prophylaxis with a 5-HT3 antagonist (granisetron or ondansetron or palonosetron or tropisetron) ± dexamethasone ± aprepitant is recommended for children receiving highly or moderately emetogenic chemotherapy. For children receiving chemotherapy of low emetogenicity, a 5-HT3 antagonist is recommended. Conclusions: The findings of several randomized trials were used to update recommendations for the prevention of acute CINV. However, significant research gaps remain and must be addressed before CINV control in children can be optimized.