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Background: Infective endocarditis secondary to Mycobacterium chimaera can present with classical constitutional symptoms of infective endocarditis but can be blood culture negative and without vegetations on transthoracic or transoesophageal echocardiogram. Patients with prosthetic valves are at particularly high risk., Case Summary: We present two patients who were diagnosed with infective endocarditis secondary to M. chimaera infection. They presented similarly with pyrexia of unknown origin and night sweats. Both patients had previously undergone aortic valve replacement; one with a tissue valve and the other with a metallic valve. New cardiac murmurs were evident on auscultation, but clinical examination showed no peripheral stigmata of endocarditis. Transoesophageal echo and transthoracic echo were both unremarkable, as were serial blood cultures. FDG PET CT scan was the key investigation, which showed increased uptake in the spleen beside other areas. Histopathology and mycobacterial cultures confirmed the diagnosis of M. chimaera infection in both cases. The first patient completed medical therapy and is now fit and well. However, the second patient unfortunately developed disseminated infection causing death., Discussion: The management of M. chimaera infective endocarditis is challenging, often with delayed diagnosis and poor outcomes. In the context of negative blood cultures and inconclusive echocardiograms where there remains a high index of suspicion for endocarditis, FDG PET CT scanning can be a crucial diagnostic importance and should be considered early in patients with prosthetic valves., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)