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In spite of the substantial role of Clostridium difficile in causing diarrhea in piglets, there have been few reports of the disease caused by this bacterium in Rio Grande do Sul, Brazil. In this paper, we describe an outbreak of C. difficile-associated diarrhea in a pig farm in Brazil. The diarrhea rate increased in piglets 1-to-7 days old from an average of 2% to approximately 20%. Necropsied piglets showed mesocolon edema, and in a histological evaluation, severe necrotizing neutrophilic colitis was observed. The intestinal contents were positive for the A/B toxins of C. difficile and negative for other tested enteropathogens. The association between the clinical signs, post mortem findings and laboratory exams confirmed the diagnosis of C. difficile-associated diarrhea. The present report confirms C. difficile as a pathogen in swine in Brazil and highlights the need for up to date routine laboratory protocols for the diagnosis of this disease in swine.