Background: Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal cardiomyopathy for which several promising therapies are in development. The diagnosis is frequently delayed or missed due to limited specificity of echocardiography and the traditional requirement for histologic confirmation. It has long been recognised that technetium labelled bone scintigraphy tracers can localise to myocardial amyloid deposits and use of this imaging modality for diagnosis of cardiac ATTR amyloidosis has lately been revisited. We conducted a multicentre study to ascertain the diagnostic value of bone scintigraphy in this disease. / Methods and Results: Results of bone scintigraphy and biochemical investigations were analysed from 1217 patients with suspected cardiac amyloidosis referred for evaluation in specialist centers. Among 857 patients with histologically proven amyloid (374 with endomyocardial biopsies), and 360 patients subsequently confirmed to have non amyloid cardiomyopathies, myocardial radiotracer uptake on bone scintigraphy was >99% sensitive and 86% specific for cardiac ATTR amyloid, with 'false positives' almost exclusively from uptake in patients with cardiac AL amyloidosis. Importantly, the combined findings of grade 2 or 3 myocardial radiotracer uptake on bone scintigraphy and absence of a monoclonal protein in serum or urine had a specificity and positive predictive value for cardiac ATTR amyloidosis of 100% (PPV CI 98.0-100). / Conclusions: Bone scintigraphy enables the diagnosis of cardiac ATTR amyloidosis to be made reliably without need for histology in patients who do not have a monoclonal gammopathy. We propose non-invasive diagnostic criteria for cardiac ATTR amyloidosis that are applicable to the majority of patients with this disease