We describe a case of a patient with atrial fibrillation, anticoagulated with dabigatran, that developed severe knee skin necrosis in the setting of an acute periprosthetic knee infection, after initiating low-molecular-weight heparin. A wide range of etiology hypotheses was discussed within a multidisciplinary team. The complex approach consisted of treating the underlying infection, multiple types of soft-tissue management, and stopping enoxaparin.