To compare the efficacy and safety of ondansetron versus less expensive metoclopramide in the treatment of children with persistent vomiting with acute gastroenteritis.A double-blind trial including consecutive consented patients ages 1 to 14 years was conducted in an urban infirmary setting from June 2008 through December 2008. Children were randomized to receive a single dose of intravenous ondansetron or metoclopramide. The primary efficacy outcome was the proportion of patients with cessation of vomiting shortly after completion of the study medication infusion in each group. Observed adverse effects and diarrhea frequency during admission and in follow-up were recorded to assess safety.One hundred sixty-seven previously healthy children (median age 3 years) diagnosed as having acute gastroenteritis with persistent vomiting completed treatment and observation. Cessation of vomiting was achieved in 68/84 patients (81%) of the ondansetron and 60/83 (72%) of the metoclopramide groups, P = 0.14. Mean time to complete cessation of vomiting was 39 minutes (SD 111) for ondansetron, and 61 minutes (SD 110) for metoclopramide, P = 0.2. The mean length of infirmary stay was 550 minutes (SD 427) for ondansetron and 575 minutes (SD 449) for metoclopramide, P = 0.71. Revisit rate, readmissions rate, and frequency of diarrhea after discharge were similar in the 2 treatment groups. No adverse reaction or other safety concerns were identified.In the sample size tested, intravenous metoclopramide therapy did not differ from ondansetron in the treatment of persistent vomiting for children with gastroenteritis admitted for intravenous fluid hydration.