Aim. To evaluate the efficiency and safety of two eradication therapy (ET) regimens for Helicobacter pylori infection in patients with concomitant chronic hepatitis C (CHC) in relation to the stage of liver fibrosis (LF). Subjects and methods. A prospective clinical trial was conducted in parallel groups. Group 1 included 50 HCV-negative patients with H. pylori-associated peptic ulcer of the stomach or duodenum; Group 2 consisted of 50 HCV-positive patients with H. pylori-associated peptic ulcer of the stomach or duodenum concurrent with CHC. Each group was divided in 2 subgroups according to the used triple ET (a proton pump inhibitor (PPI) in a standard dose + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily for 10 days) or sequential therapy (PPI in a standard dose + amoxicillin 1000 mg twice daily within the first 5 days and then PPI in a standard dose + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily for the next 5 days). LF was assessed using indirect elastometry. The efficiency of ET was evaluated by a breath test (after 4 weeks) and an analysis depending on intention-to-treat (ITT) and per-protocol (PP) treatments. A patients recorded adverse events in specially developed diaries. Results. The efficiency of ET was 74% (ITT) and 80.4% (PP) in Group 1 and 76 (ITT) and 79.1% (PP) in Group 2. Both groups displayed a tendency towards an 11.9—12.4% increase in the efficiency of the sequential therapy versus the classical triple (PP) one. The rate of totally found side effects was 20% in Group 1 and 28% in Group 2. During sequential therapy, the rate of side effects was lower than that during the classical one. The efficiency of ET did not significantly depend on the stage of LF. Only the presence of concomitant type 2 diabetes mellitus and the use of macrolides (12 months before treatment) significantly lowered the efficiency of ET (OR 0,21; 95% CI 0,06—0,69, p=0,0102 and OR 0,27 95% CI 0,08—0,9, p=0,0342). LF regardless of its magnitude significantly determined the risk of adverse events during ET (OR 3,33 95% CI 1,19—9,31, p=0,0217). A group at the highest risk of adverse events included patients with liver cirrhosis (OR 4,87; 95% CI 1,01—23,5, p=0,0492). Conclusion. It is appropriate to prescribe a sequential ET regimen as more effective and safe for patients with concomitant CHC during therapy for H. pylori infection-associated diseases. LF increases the risk of adverse events during ET.