Aim. To study the efficacy and safety of a two-week bismuth-based quadruple of Helicobacter pylori (Hp) infection with the inclusion of a probiotic Bifiform. Materials and methods. An open prospective comparative randomized study included 68 Hp-positive patients: 22 with a confirmed diagnosis of peptic ulcer disease, 46 with chronic gastritis, gastroduodenitis and erosions in the pylorobulbar zone. The diagnosis and Hp infection were verified by the results of endoscopic and morphological studies, as well as using the 13C-urease breath test and determination of the Hp antigen in the feces. Depending on the therapy, the patients were randomized into 2 groups: the main group was taken 2 times a day for 14 days omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg + bismuth tripotassium dicitrate 240 mg + Bifiform 2 capsules 2 times a day; control similar therapy was carried out, but without the inclusion of Bifiform. Repeated testing for Нр was carried out one month after the termination of the course of treatment. Results. When using bismuth-containing quadruple, a high frequency of Hp eradication was noted, which in the ITT analysis was 86.1 and 68.8% (p0.05) and in the PP analysis it was 93.9 and 95.7% (p0.05) in patients of the main and control groups, respectively. Side effects of drug therapy were detected in 16.7 and 43.8% (p0.05), which was the reason for the early termination of therapy as a result of their development in 5.6 and 28% (p0.05) in patients of the main and control groups, respectively. The inclusion of the probiotic Bifiform in the eradication triple therapy of Hp infection reduced the frequency of detection of colonic dysbiosis from 27.8 to 3.6% and had a positive effect on the indices of local immunity (increased content of plasma cells in the inflammatory infiltrate and a stable level of secretory immunoglobulin A in coprofiltrate). Conclusion. A prospective, comparative, randomized study has shown that when using a two-week bismuth-based quadruple the eradication rate exceeds 90%. The inclusion of Bifiform in the eradication scheme dramatically reduces the frequency of adverse events and increases patient compliance, and also maintains the protective factors of the gastrointestinal mucosa at a higher level.