Vascular prosthetic graft infection (VPGI) is associated with high mortality and morbidity. An early and accurate diagnosis is essential in order to give the most appropriate treatment. The case is presented of a 74 year old male subjected to an aortobifemoral bypass graft, with clinical suspicion of VPGI with inconclusive tests. Later on an F-FDG PET/CT study showed a pathological uptake, suggestive of periprosthetic infection, as well as an incidental pulmonary lesion, suggestive of a primary neoplasm. A new F-FDG PET/CT showed a significant improvement in the uptake by the vascular graft after prolonged antibiotic treatment. F-FDG is a promising tracer for detecting VPGI as the accumulated activated white cells at the infection site have a high demand for F-FDG, and could help define the response to antibiotic treatment.