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Background: The role of genetic factors in the etiology of gastroesophageal reflux disease (GERD) is still uncertain., Aim: To define whether the presence of reflux symptoms in first-degree relatives can affect the severity of the endoscopic picture of patients with GERD and disease evolution during follow-up., Patients/methods: A total of 1930 consecutive patients with GERD were referred for endoscopy from Trikala prefecture, had an entry endoscopy and a follow-up if needed. Before endoscopic evaluation, all patients and their first-degree relatives completed Reflux Symptom Questionnaire. Patients were followed up for 4 years with Reflux Symptom Questionnaire every 6 months., Results: A total of 258 (62.9%) patients with positive and 724 (47.6%) with negative family history of GERD had esophagitis (P<0.0001). Seventy-six (74.5%) patients with more than 1 family member with GERD had esophagitis (P<0.0001). During follow-up endoscopic picture was aggravated in 101 (25%) patients with positive and 46 (3%) with negative family history. A total of 359 (24%) of GERD patients with negative and 24 (10%) with positive family history managed to stop proton pump inhibitors during follow-up (P<0.0001). In logistic regression analysis: age, male sex, presence of hiatal hernia, family history of GERD, tranquilizer use, frequency, and duration of reflux symptoms were independently associated with presence of esophagitis., Conclusions: Although we cannot overlook the importance of confounding factors such as body weight and/or psychological factors, we found that endoscopic picture is more severe among GERD patients with at least 1 first-degree relative with GERD. During follow-up, patients with negative family history had more chances to wean off proton pump inhibitors after life-style modifications.