Celiac disease is the most important cause of intestinal villous atrophy. Seronegative intestinal villous atrophy, including those that are nonresponsive to a gluten-free diet, is a diagnostic challenge. In these cases, before establishing the diagnosis of seronegative celiac disease, alternative etiologies of atrophic enteropathy should be considered. Recently, a new clinical entity responsible for seronegative villous atrophy was described-olmesartan-induced sprue-like enteropathy. Herein, we report two uncommon cases of atrophic enteropathy in patients with arterial hypertension under olmesartan, who presented with severe chronic diarrhea and significant involuntary weight loss. Further investigation revealed intestinal villous atrophy and intraepithelial lymphocytosis. Celiac disease and other causes of villous atrophy were ruled out. Drug-induced enteropathy was suspected and clinical improvement and histologic recovery were verified after olmesartan withdrawal. These cases highlight the importance for clinicians to maintain a high index of suspicion for olmesartan as a precipitant of sprue-like enteropathy.