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Guidelines recommend oral rehydration therapy (ORT) and avoidance of laboratory tests and intravenous fluids for mild to moderate dehydration in children with gastroenteritis; oral ondansetron has been shown to be an effective adjunct.The aim of this study was to determine if a triage-based, nurse-initiated protocol for early provision of ondansetron and ORT could safely improve the care of pediatric emergency department (ED) patients with symptoms of gastroenteritis.This study evaluated a protocol prompting triage nurses to assess dehydration in gastroenteritis patients and initiate ondansetron and ORT if indicated. Otherwise well patients aged 6 months to 5 years with symptoms of gastroenteritis were eligible. Prospective postintervention data were compared with retrospective, preintervention control subjects.One hundred twenty-eight (81 postintervention and 47 preintervention) patients were analyzed; average age was 2.1 years. Ondansetron use increased from 36% to 75% (P < 0.001). Time to ondansetron decreased from 60 minutes to 30 minutes (P = 0.004). Documented ORT increased from 51% to 100% (P < 0.001). Blood testing decreased from 37% to 21% (P = 0.007); intravenous fluid decreased from 23% to 9% (P = 0.03). Fifty-two percent of postintervention patients were discharged with prescriptions for ondansetron. There were no significant changes in ED length of stay, admissions, or unscheduled return to care.A triage nurse–initiated protocol for early use of oral ondansetron and ORT in children with evidence of gastroenteritis is associated with increased and earlier use of ondansetron and ORT and decreased use of IV fluids and blood testing without lengthening ED stays or increasing rates of admission or unscheduled return to care.