Background: In this study, we aimed to evaluate whether waterpipe smoking can be associated with the transmission of Helicobacter pylori infection or not. Materials and Methods: Between March 2018 and April 2019, 445 patients aged over 18 years old who were admitted to outpatient clinics with dyspeptic complaints were recruited for the study. Patients are divided into two groups - Group 1 is H. pylori-positive patients and Group 2 is negative. Waterpipe smoking, smoking, age, gender, and educational status were compared among groups. Results: Two hundred and sixty-one women (58%) and 184 men (42%), totally 445 patients, tested for H. pylori infection. Seventy-nine of 261 (30%) women and 60 of 184 (32%) men had H. pylori positive. One hundred and sixty-two of 445 (36%) patients were smoking cigarette and 66 of 445 (14%) patients were using waterpipe tobacco. Waterpipe smoking individuals were found to be associated with the H. pylori positivity (P < 0.001); whereas, age, gender, educational level, and smoking were not found to be statistically significant (all P > 0.05). In binary logistic regression analysis, waterpipe tobacco smoking was found to be the only independent predictor of H. pylori infection (P < 0.001, odds ratio = 5.51, confidence interval: 3.158-9.617). Conclusion: Waterpipe smoking seems to be an important risk factor for H. pylori infection and may be one of the reasons of high prevalence of H. pylori infection.