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