AIMS : Myocardial ischaemic burden (IB) is used for the risk stratification of patients with coronary artery disease (CAD). This study sought to define a prognostic threshold for quantitative [15O]H2O positron emission tomography (PET)-derived IB. METHODS AND RESULTS : A total of 623 patients with suspected or known CAD who underwent [15O]H2O PET perfusion imaging were included. The endpoint was a composite of death and non-fatal myocardial infarction (MI). A hyperaemic myocardial blood flow (hMBF) and myocardial flow reserve (MFR)-derived IB were determined. During a median follow-up time of 6.7 years, 62 patients experienced an endpoint. A hMBF IB of 24% and MFR IB of 28% were identified as prognostic thresholds. Patients with a high hMBF or MFR IB (above threshold) had worse outcome compared to patients with a low hMBF IB [annualized event rates (AER): 2.8% vs. 0.6%, P < 0.001] or low MFR IB [AER: 2.4% vs. 0.6%, P < 0.001]. Patients with a concordant high IB had the worst outcome (AER: 3.1%), whereas patients with a concordant low or discordant IB result had similar and low AERs of 0.5% and 0.9% (P = 0.953), respectively. Both thresholds were of prognostic value beyond clinical characteristics, however, only the hMBF IB threshold remained predictive when adjusted for clinical characteristics and combined use of the hMBF and MFR thresholds. CONCLUSION : A hMBF IB ≥24% was a stronger predictor of adverse outcome than an MFR IB ≥28%. Nevertheless, classifying patients according to concordance of IB result allowed for the identification of low- and high-risk patients.