Acute gastroenteritis (AGE) is one of the most frequent reasons for young children to visit emergency departments (EDs). We aimed to evaluate (1) feasibility of a nurse-guided clinical decision support system for rehydration treatment in children with AGE and (2) the impact on diagnostics, treatment, and costs compared with usual care by attending physician. A randomized controlled trial was performed in 222 children, aged 1 month to 5 years at the ED of the Erasmus MC-Sophia Children’s hospital in The Netherlands ( 2010–2012). Outcome included (1) feasibility, measured by compliance of the nurses, and (2) length of stay (LOS) at the ED, the number of diagnostic tests, treatment, follow-up, and costs. Due to failure of post-ED weight measurement, we could not evaluate weight difference as measure for dehydration. Patient characteristics were comparable between the intervention (N = 113) and the usual care group (N = 109). Implementation of the clinical decision support system proved a high compliance rate. The standardized use of oral ORS (oral rehydration solution) significantly increased from 52 to 65%(RR2.2, 95%CI 1.09–4.31 p < 0.05). We observed no differences in other outcome measures.Conclusion: Implementation of nurse-guided clinical decision support system on rehydration treatment in children with AGE showed high compliance and increase standardized use of ORS, without differences in other outcome measures.What is Known:• Acute gastroenteritis is one of the most frequently encountered problems in pediatric emergency departments.• Guidelines advocate standardized oral treatment in children with mild to moderate dehydration, but appear to be applied infrequently in clinical practice.What is New:• Implementation of a nurse-guided clinical decision support system on treatment of AGE in young children showed good feasibility, resulting in a more standardized ORS use in children with mild to moderate dehydration, compared to usual care.• Given the challenges to perform research in emergency care setting, the ED should be experienced and adequately equipped, especially during peak times.