Background: Gastroesophageal reflux (GERD), in particular extra-esophageal reflux, has been associated with a variety of upper aerodigestive tract symptoms or diseases such as sinusitis and otitis. Many studies showed the role of reflux in chronic otitis media with effusion in children. Objective: To investigate the relationship between gastro-esophageal reflux diseases (GERD) and otitis media with effusion (OME) by evaluation of the presence of gastric pepsinogen in middle ear fluid of patients with OME. Patients and methods: Prospective study was conducted on 24 patients. Those patients suffered from recurrent otitis media with effusion, undergoing bilateral myringotomy with ventilation tube insertion and middle ear effusions, as well as blood samples were collected. All cases were subjected to history taking and ENT examination. Total pepsinogen concentrations of effusions and serum samples were measured with an enzyme-linked immuno sorbent assay (ELISA) using Human Pepsinogen I ELISA Kit (CUSABIO, USA). Results: The mean age of the included cases were 32.7 years. Patients were 25 females (62.5%) and 15 males (37.5%). The mean value of GERD score was 11.18 (range, 10 – 12). The four tympanogram types did not differ in age and gender. All the cases with type B and C tympanometry in the right ear was with GERD score of 11 and 12. Conclusion: GERD is considered as one of the contributing factors in the etiopathogenesis of middle ear effusion.