Gastro oesophageal reflux disease is due to involuntary gastric contents reflux into the esophagus from stomach, causing heartburn and acid regurgitation symptoms. Genetic and environmental factors are important factors in the causation of disease. Human Leukocyte antigens considered as an excellent marker for population genetics analysis and disease association. This study aimed to investigate the association between HLA-DRB1-DQB1 haplotype that inherited in linkage and its association with gastro oesophageal reflux disease (GERD). Patients and healthy controls were prospectively recruited from gastrocolonoscope unit at Al-Kindy Teaching Hospital (Baghdad-Iraq) between January and July 2016. Forty Iraqi Arab Muslims patients with a history of heartburn and dyspepsia compared with 100 Iraqi Arab Muslims control. All study patients and control group underwent upper gastroesophageal endoscope examination and HLA-DRB1 and HLA-DQB1 genotype were done using sequence spesific oligonucleotide primer to both groups. The frequencies of two haplotype HLA-DRB1⁄03-DQB1⁄03 and HLADRB1⁄ 13-DQB1⁄06 were significantly higher in patients with GERD while haplotype HLA-DRB1⁄03-DQB1⁄02 was significantly higher in control group. Sex had an effect in disease developing that haplotype HLADRB1⁄ 03-DQB1⁄03 was significantly more common in female patients that increased susceptibility to disease. This study identified that two haplotypes HLA-DRB1⁄03- DQB1⁄03 and HLA-DRB1⁄13- DQB1⁄06 leads to increased susceptibility to GERD and haplotype HLA-DRB1⁄03-DQB1⁄02 was protective against GERD development.