Background: More than 50% of the adult population all over the world are infected with H. pylori. H. pylori infection is a significant reason for chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric carcinoma. Diagnosis can be achieved by invasive (endoscopic-based) and non- invasive (urea breath test, H. pylori stool antigen test and IgG antibodies) methods. Objective: Comparison between different methods for diagnosis of H. pylori infection. Methodology: This study included 118 patients attending Gastrointestinal Endoscopy Unit at Zagazig University Hospitals. Samples included biopsies, stool, and blood. Biopsies were assessed by Polymerase Chain Reaction (PCR) through amplification of ureC (glmM) gene and rapid urease test (RUT). Stool samples were processed for analysis by stool antigen test (SAT) ELISA kit. H. pylori IgG antibodies were detected by Helicobacter pylori IgG ELISA kit. Results: The percentages of positive cases of all tests used were as follows; RUT (67.8%), PCR (50%), RUT and PCR (gold standard) (5.7%), SAT (57.6%), IgG antibodies (51.69%) and combined SAT with IgG antibodies (36.4%). The sensitivities and specificities were as follows; RUT (100%, 59 %), PCR (100%, 92.18%), SAT (77.77%, 59.3%), IgG antibodies (50%, 46.87%) and combined stool antigen test with IgG antibodies (42.59%, 68.7%). Conclusion: Invasive tests were more accurate than non-invasive tests for diagnosis of H. pylori-infected patients. Non- invasive test may be used for follow up after treatment of H. pylori infection. Combination of SAT with anti-H.pylori IgG antibodies improves the specificity and the accuracy as compared to anti-H.pylori IgG antibodies alone but improves the specificity only when compared to SAT alone.