Proximal gastric vagotomy and intermittent and maintenance therapy with H2-antagonists have all been claimed to be effective in long-term management of duodenal ulcer disease. The model of a Markov chain was used to compare their costs by a medical decision analysis. The high price of the initial procedure made proximal gastric vagotomy the most expensive therapy, its costs rising from +10,600 after 1 yr to +12,200 after 15 yr. The average costs of intermittent therapy per patient rose from +500 to +7500. Maintenance therapy cost as much as intermittent therapy but provided 8% and 4% more time spent free of ulcer relapse and pain, respectively. In a sensitivity analysis, the order of the therapeutic options regarding their cost-effectiveness remained robust to changes in the assumptions underlying the model. In a European health care system, the initial surgical procedure cost only one-seventh of the average annual income compared with two-thirds in the United States, and proximal gastric vagotomy turned out to be the cheapest therapy after 6 yr. These results suggest that maintenance therapy provides the best long-term management. Gastric surgery may represent a cost-effective measure of ulcer prevention in Europe but not in the United States.