Background: Functional gastrointestinal disorders in infants and toddlers are common worldwide and cover a variety of disorders associated with chronic, recurrent symptoms attributable to the gastrointestinal tract, but not explained by structural or biochemical abnormalities. Objectives: This study aimed to explore the main predictors for reflux disease improvements among infants. Methodology: This cross-sectional study recruited 300 infants with reflux manifestations from the outpatient clinic of the Pediatrics Department at Aswan University Hospital from January 2021 till December 2022. Results: after adjusting for age and sex, the main independent predictors for GERD improvement among the studied cohort were weight, length, skin manifestation, growth faltering, CoMiSS score at baseline and at 3rd visit. Conclusion: When CoMiSs negative the AR formula more evident than PPI finally domperidine having the least impact on improving GERD symptoms. 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.