Background: The extent of antibiotic resistance among Helicobacter pylori strains infl uences current clinical therapeutic regimens in each region. Objectives: This cross-sectional study aimed to determine the resistance property and minimum inhibitory concentration (MIC50-90) of Helicobacter pylori strains toward metronidazole, clarithromycin, and ciprofl oxacin in patients with distinct gastric histopathological changes in Tehran, Iran. Methods: This study was conducted on 170 patients suff ering from gastric complications in three hospitals in Tehran from October 2014 until March 2015. Two separate biopsy samples were collected from each patient and used for pathological and microbiological examinations. Antimicrobial susceptibility tests were performed by agar dilution method according to the CLSI guidelines. The MIC values and susceptibility to varying concentrations of metronidazole (4 to 64 g/mL), ciprofl oxacin (0. 5 to 16 g/mL), and clarithromycin (0. 25 to 16 g/mL) were determined based on EUCAST recommendations. Results: Our results indicated the infection with H. pylori in a frequency of 32% (55/170) among the study patients (female, 51% and male, 49%). Endoscopic fi ndings indicated that 42% of the patients suff ered from peptic ulcers, 33% from duodenal ulcers, and 25% with a non-ulcer disease. Pathological fi ndings indicated 58% of the patients had chronic gastritis, 33% had active chronic gastritis, and 9% suff ered from intestinal metaplasia. In terms of antibiotic susceptibility, nearly 76. 3%, 49%, and 45. 5% of the strains were resistant to metronidazole, clarithromycin, and ciprofl oxacin, respectively. The MIC values at which the growth of 50% and 90% of the strains was inhibited (MIC50-90) were 32-64 g/mL for metronidazole, 0. 5-16 g/mL for clarithromycin, and 2-16 g/mL for ciprofl oxacin. Conclusions: The overall resistance levels were relatively high among the study patients. Accordingly, the administration of other anti-Helicobacter drugs, as well as more appropriate therapeutic regimens based on laboratory results, is recommended in patients with a history of treatment failure.