Peptic ulcer disease affects around 5-10% of the general population of the world and is an important cause of morbidity and mortality throughout the world. Currently researchers have shown that there is an association between the ABO/Rh blood group and peptic ulcer disease. However, such studies are limited in Ethiopia. The purpose of this study was to assess the association between ABO/Rh blood group distribution and associated risk factors with the incidence of peptic ulcer disease at Felege Hiwot Comprehensive Referral Hospital (FHCRH) Bahir Dar. Hospital based cross-sectional study was carried out from February to April 2023. Peptic ulcer disease patients were selected for the test; non-peptic ulcer disease patients, hospital staffs, and students were recruited as a control group. Blood was collected from study participants and their ABO/Rh blood types were identified and stool collected from each participant and check the presence of H.pylory and recorded. Structured questionnaire was also used to collect other relevant data. The data were entered in to Epi Data software version 3.1 and analyzed using SPSS version 23. Totally172 subjects (108 male and 64 female), ranging in age. The ABO blood group frequency in peptic ulcer patients was 32.55% (28/86) ,23.26% (20/86),6.98% (6/86),37.20% (32/86)for blood group A, B AB and O.While for control group 34.89%(30/86),11.62%(10/86),8.13%(7/86),45.34%(39/86) for blood group A, B, AB and O. Rh positivity was found in 93.02% (80/86) of peptic ulcer disease patients and 97.67% (84/86) of controls. Among peptic ulcer patients 65.11% (56/86) had Duodenal ulcer and 34.89% (30/86) Gastric ulcer Patients with blood group O were found to have a higher percent 46.51% (40/86), of H.Pylori infection than other blood groups. There was statically significant Chi-square association between sex {P=0.001, AOR (95%CI) 3.99 (2.98, 6.93)}, use of NSAIDs {=0.001, AOR (95%), 2.4 (0.44, 0.41), smoking cigarette {p=0.014, AOR (95%) 6.86 (1.52, 32.63)} alcohol consumption {P=0.032, AOR (95%CI), 3.02 (1.43, 7.01)}, and peptic ulcer disease. Peptic ulcer disease is more prevalent among patients with blood group O than other blood group types. Additionally, blood group O had a higher percent of H.Pylori infection than other blood group types. Use of NSAIDs, Smoking and Alcohol consumption were risk factors for peptic ulcer disease. Keywords: ABO/Rh blood group, Peptic ulcer disease, Gastric ulcer, Duodenal ulcer, NSAIDs.