Microscopic colitis causes chronic watery diarrhea. Many cases may be induced by medications, and lansoprazole, a commonly used proton-pump inhibitor, has been associated with collagenous colitis and lymphocytic colitis, the two subtypes of microscopic colitis. Two cases of collagenous colitis associated with lansoprazole are reported, both in older female patients, who each developed profuse watery diarrhea within weeks of starting lansoprazole to treat upper digestive disorders. Colonoscopy was normal and biopsies demonstrated typical features of collagenous colitis. There was a rapid clinical improvement upon switching from lansoprazole to rabeprazole, and histological normalization on follow-up biopsies. A review of the literature showed 14 other cases of lansoprazole-related microscopic colitis. There are no reported cases of microscopic colitis associated with other proton-pump inhibitors, suggesting a pathophysiologic mechanism specific to the pharmacology of lansoprazole. Clinicians must be aware of this association when prescribing this medication; when a patient taking lansoprazole develops diarrhea, substituting an alternative proton-pump inhibitor should allow resolution of the diarrhea.