Helicobacter pylori infection is a common bacterial infection in humans and is associated with peptic ulcer disease and chronic gastritis. The presence of natural resistance to some antibiotics in bacteria, as well as the appearance of primary and secondary resistance to antibacterial agents, complicates treatment and determines the search for new methods of therapy. The aim of this study was to evaluate the efficacy and safety of 10-year complex treatment of patients with duodenal ulcer associated with H.pylori , 136 patients (96 men, 40 women; mean age 45.8 14.8 years; 18-65 years). H.pylori was determined morphologically and by rapid urease test one day before the start of therapy, after 1, 6, 12 months, 2 years, 5 and 10 years. Patients of the first group received basic therapy: omeprazole 0.02 g 2 times a day, clarithromycin 0.5 g 2 times a day, amoxicillin 1 g 2 times a day, for 10 days (OCA group 1; n = 98). Patients of the second group, in addition to the basic therapy, took 1 mg per day drug Liсopid (group 2 OСAL; n = 38). At the 1st stage of the clinical study, 130 patients completed eradication therapy. Tracking completeness was 96 %. The frequency of H.pylori eradication after per protocol treatment: OCA - 83 % (95 % CI: 75 %-91 %), OCAL - 97 % (95 % confidence interval (CI): 92 %-100 %). The incidence of adverse reactions after treatment (per protocol): OCA - 26 % (95 % CI: 17-35 %; nausea; n = 24), discontinued treatment - 5 % (95 % CI: 0.8 %-10 %; diarrhea; n = 5); OCAL - 3 % (95 % CI: 0.01 %-8 %; nausea; n = 1), all were treated. Taking the drug Liсopid 1 mg (glucosaminyl muramyl dipeptide, JSC Peptek, Russia) as part of complex therapy contributed to the elimination of H.pylori and the absence of relapses for 2 years. Observation of patients in the next 5 and 10 years also showed the advantage of including the immunomodulator in therapy: a significant 15 % decrease in H.pylori reinfection (P 0.05), a 23 % decrease in the frequency of gastrointestinal adverse reactions (P0.01), compared with a 10-day standard triple regimen without immunomodulatory therapy with glucosaminylmuramyl dipeptide. When using several antibiotics in H.pylori eradication therapy, not only pathogenic, but also commensal microorganisms are destroyed, the waste products of which are vital and maintain immune homeostasis, including through the NOD2 receptors of innate immunity. The effectiveness of the complex therapy of H.pylori infection can be explained by the fact that the drug Liсopid compensates for the signal for innate immunity receptors that is missing due to the absence of commensals, providing an adequate immune response and preventing chronicity and recurrence of infection.