Reactive arthritis usually presents as a sterile, inflammatory, asymmetric oligoarthritis, affecting large lower extremity joints. Extra-articular features (conjunctivitis, uveitis, enthesopathy, urethritis, balanitis, keratoderma blenorrhagicum) may occur. Common causes of enteric reactive arthritis are preceding infections attributable to Salmonella, Shigella, Campylobacter, and Yersinia. In contrast, Clostridium difficile is an uncommon cause of reactive arthritis, with only approximately 40 reported cases. We describe a patient with an intense additive, asymmetric oligoarthritis after an antecedent C. difficile infection. The potential contribution of C. difficile to more insidious cases of undifferentiated oligoarthritis is discussed, with emphasis on corresponding therapeutic interventions.