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Helicobacter pylori (H. pylori) is one of the most common chronic bacterial infections in humans, affecting half of world's population. Therapy for H. pylori infection has proven to be both effective and safe. The one-week triple therapy including proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole is still recommended as a first-line treatment to eradicate H. pylori infection in countries with low clarithromycin resistance. Generally, this therapy is well-tolerated, with only a few and usually minor side effects. However, rare but severe adverse effects such as pseudomembranous colitis have been reported, Clostridium difficile (C. difficile) infection being the main causative factor in all cases. We report the cases of two women who developed pseudomembranous colitis after a 1-wk triple therapy consisting of pantoprazole 20 mg bid, clarithromycin 500 mg bid, and amoxicillin 1 g bid to eradicate H. pylori infection. A limited colonoscopy showed typical appearance of pseudomembranous colitis, and the stool test for C. difficile toxins was positive. Rapid resolution of symptoms and negative C. difficile toxins were obtained in both patients with oral vancomycin. No relapse occurred during a four and eleven-month, respectively, follow up. These cases suggest that physicians should have a high index of suspicion for pseudomembranous colitis when evaluate patients with diarrhea following H. pylori eradication therapy.