Background/Aim. To identify the etiological role ofHelicobacter pylori(Hp) and nonsteroidal anti-inflammatory drugs (NSAIDs) in endoscopically diagnosed duodenal ulcers (DUs).Methods. Patients undergoing esophagogastroduodenoscopy in two major hospitals in Antalya and Adiyaman were included in this study and assigned as duodenal ulcer (n=152; median age: 41.0 (16–71) years; 58.6% males) or control group (n=70; median age: 41.0 (18–68) years; 57.1% males). Patient demographics, risk factors, and NSAID/acetylsalicylic acid (ASA) use were recorded.Results.HPwas more commonly located in the corpus (75.0 versus 50.0%; odds ratio [OR] = 3.00; 95% confidence interval [CI]: 1.66–5.44;P<0.001), incisura (75.7 versus 60.0%;OR=2.07; 95% CI: 1.13–3.79;P=0.017), and antrum (80.3 versus 60.0%;OR=2.71; 95% CI: 1.45–5.05;P=0.001) among DU patients than controls.Hppositivity was 84.9% whileHpwas negative in 15.1% of patients including those accompanied with NSAID and/or ASA use (9.2%), and those were negative for all three etiological factors (5.9%).Conclusion. Our findings indicate the substantial role ofHpin the pathogenesis of DU disease as identified in 84.9% of DU patients compatible with the background prevalence of 61.4% among age-matched control subjects.Hpwas the single causative factor in 44.1% of our patients, while NSAID/ASA exposure was in 9.2%.