The most commonly used regimen for Helicobacter pylori therapy at present is twice-daily proton pump inhibitor (PPI)-based triple therapy. Bismuth-based therapy is the next most common treatment used by gastroenterologists. When a PPI is combined with bismuth-based triple therapy (quadruple therapy), eradication rates are increased as compared with the triple therapy alone. Three separate randomized trials from three continents that compare quadruple therapy and PPIbased triple therapy revealed remarkably similar results. Eradication rates with PPI-based triple therapy and quadruple therapy were not significantly different. The eradication rates with quadruple therapy were 3% to 6% higher than PPI triple therapy, indicating that quadruple therapy should be no less effective than PPI triple therapy. Furthermore, these two therapies had similar rates of compliance and adverse events.