Objective. To assess efficacy and safety of 14-day triple nifuratel-based therapy compared to 14-day standard triple therapy in adult patients with symptomatic H. pylori infection. Materials and Methods. A total of 70 patients with dyspepsia and microbiologically confirmed H. pylori infection were enrolled into the open-label, randomized, comparative clinical trial. The study group (n = 35) received a 14-day triple nifuratel-based therapy: esomeprazole (20 mg BID), nifuratel (400 mg BID) and amoxicillin (1000 mg BID). The comparator group (n = 35) received 14-day conventional clarithromycinbased triple therapy: esomeprazole (20 mg BID), clarithromycin (500 mg BID) and amoxicillin (1000 mg BID). Eradication of H. pylori was assessed using stool antigen test. Results. Eradication rates for 14-day nifuratel-based triple therapy and 14-day clarithromycin-based triple therapy in the intent-to-treat (ITT) population were 82.9% and 74.3% (p = 0.561), respectively. In the per-protocol (PP) population, eradication rates were 90.6% and 89.7% (p = 1.00), respectively. Adverse events were reported in 17.1% of patients in the study group and 34.3% of patients in the comparator group (p > 0.05). Conclusions. The 14-day triple nifuratel-based therapy has demonstrated a high H. pylori eradication rate (above 90%). Nifuratel triple therapy may be considered as an alternative to clarithromycin-based triple therapy for patients with a history of the prior macrolide exposure or macrolide intolerance.