<b><i>Introduction:</i></b> Obesity is a well-known risk factor for a variety of gastrointestinal disorders (GID). <i>Helicobacter pylori</i> is associated with different GID, such as gastric cancer and chronic gastritis. In this study, we investigated the prevalence of dominant genotypes in <i>H</i>. <i>pylori</i> isolated from obese patients diagnosed with gastric ulcer, duodenal ulcer, and gastric cancer. <b><i>Methods:</i></b> A total of 222 <i>H</i>. <i>pylori</i>-positive samples were collected from patients with obesity. GID and gastric cancer were identified by endoscopy and histopathology, respectively. Three biopsy specimens from the gastric antrum were obtained from each patient for culture tests, histological examination, and identification of vacuolating cytotoxin A (<i>vacA</i>) (<i>vacA</i> s1, <i>vacA</i> s2, <i>vacA</i> m1, <i>vacA</i> m2, <i>vacA</i> s1m1 <i>vacA</i> s1m2, <i>vacA</i> s2m1<i>,</i> and <i>vacA</i> s2m2), <i>cagA</i>, <i>cagE</i>, <i>iceA1</i>, <i>oipA</i>, <i>dupA</i>, and <i>babA2</i> using polymerase chain reaction. <b><i>Results:</i></b> <i>vacA</i>, <i>cagE</i>, <i>cagA</i>, <i>iceA1</i>, <i>oipA</i>, <i>dupA</i>, and <i>babA2</i> genes were detected in 222 (100%), 171 (77%), 161 (72.5%), 77 (34.6%), 77 (34.6%), 137 (61%), and 69 (31%) patients with obesity, respectively. Our findings revealed that <i>vacA</i>, <i>iceA1</i>, <i>oipA</i>, and <i>babA2</i> were significantly associated with a higher risk of GID, while <i>cagE</i>, <i>cagA</i>, and <i>dupA</i> indicated no correlation with the development of GID. Also, in the combination of s- and m-region genotypes, s1m2 (79%) was the most frequently identified genotype in patients with obesity. A significant association was also found between <i>cagA</i> and the presence of <i>vacA</i> genotypes (except for <i>vacA m1</i> and <i>babA2</i>). <b><i>Conclusions:</i></b> This study indicated the high prevalence of different virulence genes in <i>H. pylori</i> isolated from obese patients and supported the significant role of <i>H. pylori</i> in the development of GID.

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