Objective: The aim of this study is to compare the efficacy of oral ondansetron with oral domperidone in reducing vomiting in children with acute diarrhea. Study Design: Randomized control trial Place and Duration:The study was conducted atChildren Medical Center (CMC) / Dr Habibun Nabi Children Hospital, Airport Road Mingora Swat and Paediatrics department of Central Park Teaching Hospital, Lahore during the period fromJanuary 2020 to September 2020. Methods: Total one hundred and fifty children with ages 1-7 years were presented in this study. Children had diarrhea and vomiting from the last 24-48 hours. Informed written consent was taken from guardians for detailed demographics age, sex, weight, height and residency were calculated. Children were equally split into two groups. Group A received 0.15 mg/kg oral ondansetron with 75 children and group B received 0.5 mg/kg oral domperidone with 75 patients. Post treatment blockage of vomiting was observed after 12-24 hours. SPSS 24.0 version was used to analyze all data. Results: Majority of the patients were males 45 (60%) in group A and 42 (56%) in group B while rest were females 30 (40%) in group A and 33 (44%) in group B. Mean age of the patients in group A was 4.3 ±2.17 years and in group B mean age was 3.08±6.88 years. Mean weight of the patients were 15.07±8.23 kg and 15.02±3.09 kg in group A and B respectively. In group A mean height was 98.07±11.14 cm and in group B mean height was 97.67±18.24 cm. After 12 hours vomiting stopped in group A was 61 (81.3%) and 54 (72%) patients in group B. Efficacy after 24 hours were significantly higher among patients of group A in 69 (92%) children as compared to group B in 60 (80%) cases with p value < 0.05. Conclusion: In this study we concluded that for reducing vomiting in children with acute diarrhea use of oral ondansetron was effective and useful as compared to oral domperidone. Keywords: Acute Diarrhea, Ondansetron, Domperidone, Vomiting