Background: Gastroesophageal reflux (GER) is the passage of the gastric contents into the esophagus, with or without regurgitation and/or vomiting. Nutritional management is recommended as a first-line approach in infants, while in children, a therapeutic trial with antacid medication is advised for early management. Objectives: This study aimed to compare the effect of cow's milk protein eliminated diet versus various medical treatment interventions in management of infant reflux. Methodology: This double-blinded randomized controlled trial (RCT) study included 300 infants presented with manifestations of GERD presented to the outpatient clinic of the Pediatrics Department at Aswan University Hospital in the period from January 2021 till December 2022. Results: The relationship between CoMiSs results and improvement of GERD symptoms in groups V and IV, most cases with CoMiSs positive (89% and 87.5%) showed improvement in GERD symptoms and the CoMiSs negative cases showed minimal improvement (12.5% and 7.1%). On the other hand, for cases in group III, improvement was higher in CoMiSs negative cases (53%) compared with CoMiss positive cases only 6.7%, and this was statistically significant (p=0.001). Contrarily, among Groups I and II, rate of improvement was higher among CoMiSs negative patients (22% and 65 %) compared with CoMiSs positive only (5% and 12%). These differences were statistically significant. Conclusion: CoMiSS Score is a simple, fast, and easy-to-use useful tool for screening infants who presented with recurrent or persistent GI manifestations including GERD symptoms.