In the treatment of Helicobacter pylori-associated peptic ulcer disease, the complexity (ie, frequency and duration) of drug administration, the presence or development of bacterial antibiotic resistance, and the occurrence of side effects influence patient compliance and eradication rates, which consequently affect the costs of treatment regimens. The National Institutes of Health Consensus Conference and 1997 Digestive Health Initiative Update Conference have recommended that all patients with gastric or duodenal ulcer and H pylori infection, whether on first presentation or recurrence, be treated with antimicrobials. However, H pylori resistance to antimicrobials, specifically to nitroimidazole compounds, has resulted in varied and decreasing success rates of treatment regimens. Comparing the efficacy, safety, and costs of current treatment strategies for the eradication of H pylori, a combination triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin is recommended as an effective alternative to standard bismuth-based triple therapy. When compared with other therapies, these offer more rapid symptomatic relief, improved tolerability, increased compliance and efficacy, and moderate costs.