Peptic ulcer (PU) disease has a high rate of occurrence and recurrence in Korean and the selection of drug for treatment is diverse. In this study, the therapeutical effectiveness of regimens including proton pump inhibitors (PPI) was compared with the single PPI therapy. The clinical data were collected from 1,658 patients having idiopathic or drug-induced PU complication from a Medical Center in Daegu, Korea, and analyzed retrospectively based on the results of endoscopic examination, the drug history and the therapeutic cost depending on drugs used. The comparison of complete healing rate and recurrence rate showed no significant differences between the single PPI groups and the combination group with antacids, prokinetic agent or mucosa protectants. However, the combination therapy of PPI with mucosa protectants gave a slightly better therapeutic outcome than single PPI treatment in gastric ulcer patients. Comparatively, the combination of PPI with antacids significantly reduced the therapeutic effectiveness in duodenal ulcer patients. The analysis of cost-based therapeutic effectiveness reveals that any economic benefits in PU treatment were not gained by the combination of other class of ulcer drugs. Even though the rapidity of healing rate was not considered, it can be concluded that the PPI combination therapy might be not desirable in PU treatment. Particularly triplet or quartet combination therapy in PPI regimen was absolutely economically ineffective therapy in spite of the increase of medication costs.