OBJECTIVES:  Eradication of Helicobacter pylori with antimicrobials and proton pump inhibitors (PPI) was recommended by Maastricht IV Consensus report for all infected patients with peptic ulcer disease. The precise regimen that should be used for eradication of the infection remains uncertain because of the variety of regimens described, variable results with the regimens, and difficulties in predicting drug compliance outside clinical trials. This research aims is to compare the cost-effectiveness of triple drug therapy with PPIs in Ukraine. METHODS:  A model analysis was developed with 1-week six regimens that are widely used for the eradication of H. pylori: amoxicillin, clarithromycin with either omeprazole or pantoprazole, lansoprazole, esomeprazole and rabeprazole; metronidazole, clarithromycin with pantoprazole. Probabilities for eradication were determined from published data. RESULTS:  Standard 1-week triple drug therapy with pantoprazole, metronidazole and clarithromycin was the least expensive strategy ($8.55), and amoxicillin, clarithromycin with esomeprazole therapy was the most expensive ($17.93). The highest eradication rates (90.5%) was achieved using 1-week regimen including rabeprazole the costs of which was $15.72. CONCLUSIONS: The regimen with esomeprazole was shown to be the most cost-effective. As the difference in costs between the therapies is significant compared with the efficacy of H. pylori eradication therapies, it is logical that the eradication strategies with low eradication rates are the most cost-effective.