Abstract. This study examines the development of antibiotic resistance in Helicobacter pylori infection and its influence on the effectiveness of eradication therapy. The clinical factors associated with treatment failure, including previous antibiotic exposure, treatment adherence, and the possible presence of antimicrobial resistance, were considered. The study also describes the molecular mechanisms of resistance and the role of microbiological and molecular diagnostic methods in identifying resistant strains. The results indicate that previous use of antibiotics, particularly macrolides and fluoroquinolones, may be associated with reduced eradication effectiveness. The study emphasizes the importance of rational antibiotic selection, individualized treatment approaches, appropriate diagnostic assessment, adherence to prescribed therapy, and confirmation of eradication after treatment. These approaches may contribute to improving therapeutic outcomes and reducing the clinical impact of antibiotic-resistant Helicobacter pylori infection.