Abstract The epidemiology of Helicobacter pylori resistance to antibiotics is poorly documented in Africa and especially in Algeria. The aim of our study was to determine the antibiotic resistance rates, as well as its possible relationship with VacA and CagA virulence markers of isolates from Algerian patients. One hundred and fifty one H. pylori isolate were obtained between 2012 and 2015 from 200 patients with upper abdominal pain. Antimicrobial susceptibility testing was performed for amoxicillin, clarithromycin, metronidazole, ciprofloxacin, rifampicin and tetracycline. Molecular identification of H. pylori and the detection of vacA and cagA genes were performed using specific primers. We found that H. pylori was present in 83.5% of collected biopsies, 54.9% of the samples were cagA positive, 49.67% were vacA s1m1, 18.30% were vacA s1m2 and 25.49% were vacA s2m2. Isolates were characterized by no resistance to amoxicillin (0%), tetracycline (0%), rifampicin (0%), a high rate of resistance to metronidazole (61.1%) and a lower rate of resistance to clarithromycin (22.8%) and ciprofloxacin (16.8%). No statically significant relationship was found between vagA and cagA genotypes and antibiotic resistance results (p > 0.5) except for the metronidazole, which had relation with the presence of cagA genotype (p = 0.001).