BACKGROUND: To assess the therapeutic effects of oral zinc supplementation on acute watery diarrhea of children with moderate dehydration. METHODS: All 9-month to 5-year-old children who were admitted with acute watery diarrhea and moderate dehydration to the Children Ward of Motahari Hospital, Urmia, Iran in 2008 were recruited. After the application of the inclusion and exclusion criteria, the patients were randomly allocated to two groups: one group to receive zinc plus oral rehydration solution (ORS) and the other one to receive ORS plus placebo. All the patients were rehydrated using ORS and then receiving ORS for ongoing loss (10 ml/kg after every defecation). Additionally, the patients in the intervention group received zinc syrup (1 mg/kg/day) divided into two doses. A detailed questionnaire was filled daily for each patient by trained pediatrics residents; it contained required demographic characteristics, nutrition and hydration status, and disease progression. The primary outcome (frequency and consistency of diarrhea) and the secondary outcomes (duration of hospitalization and change in patients' weight) were compared between the two groups. RESULTS: The mean diarrhea frequency (4.5±2.3 vs. 5.3±2.1; P=0.004) was lower in the group receiving zinc +ORS; however, the average weight was relatively similar between the two groups (10.5±3.1 vs. 10.1±2.3; P=0.14). The qualitative assessment of stool consistency also confirmed earlier improvement in the treatment group in the first three days of hospitalization (P <0.05). The mean duration of hospitalization was significantly lower in the patients receiving zinc supplements (2.5±0.7 vs. 3.3±0.8 days; P=0.001). CONCLUSION: Our results imply the beneficial effects of therapeutic zinc supplementation on disease duration and severity in patients with acute diarrhea and moderate dehydration in Iran. TRIAL REGISTRATION NUMBER: IRCT201201241580N2.