The aim of this prospective study was to evaluate the impact of obesity, determined by different anthropometric measures, on clinical and endoscopic severity of GERD and the relation between serum leptin and clinical and endoscopic severity of GERD in Egyptian patients. The study was carried out at Ain Shams University Hospitals and Theodor Bilharz Research Institute, Cairo, Egypt. A total of 60 patients with clinically and endoscopically evident gastroesophageal reflux disease (GERD) were enrolled in this study as well as 20 healthy subjects matched for age and gender serving as the control group. Patients were divided according to their body mass index (BMI) into two groups: group 1 (n = 30): overweight and obese (BMI ≥ 25 and/or waist-to-height ratio [WHtR] ≥ 0.5) and group 2 (n = 30): normal weight (BMI ≥ 18 to < 25 and/or WHtR ≥ 0.4 to < 0.5). Upper gastrointestinal endoscopy, anthropometric measures, and symptom severity score questionnaire were done for all patients. Serum leptin hormone was assessed for patients and control groups.The evidence revealed statistically significant difference between the two groups in terms of different anthropometric measures (P < 0.00) except the height (P < 0.9), abdominal fat depot equations (P < 0.00), endoscopic findings according to Los Angeles classification (P < 0.001), symptom severity score (P < 0.00), and serum leptin hormone (43.96 ± 23.50 in group 1 vs. 7.5133 ± 8.18294 in group 2 and 6.98 ± 5.90 in the control group) (P = 0.00). Obesity in general and central (abdominal) obesity specifically has significant impact on clinical and endoscopic severity of GERD. Increased leptin hormone level is associated with clinical and endoscopic severity of GERD. Future trial on larger number of patients is emphasized.