AIMS: The aim of this study was to explore the relationships between ischaemic burden and changes in absolute myocardial perfusion following chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS AND RESULTS: A total of 193 consecutive patients underwent [15O]H2O positron emission tomography prior to and three months after successful CTO PCI. Change in perfusion defect size, quantitative hyperaemic myocardial blood flow (MBF) and coronary flow reserve (CFR) within the CTO area were compared among patients with limited (0-1 segment, N=15), moderate (2-3 segments, N=61) and large (≥4 segments, N=117) perfusion defects. Median reductions in defect size were 1 [0-1], 2 [1-3], and 4 [2-5] segments in patients with a limited, moderate and large defect (all comparisons p<0.01). Hyperaemic MBF and CFR improved significantly regardless of baseline defect size (overall between groups p=0.45 and p=0.55). After stratification of patients to a low, intermediate or high tertile according to baseline hyperaemic MBF or CFR levels, changes in hyperaemic MBF and CFR after CTO PCI were comparable between tertiles (overall p=0.75 and p=0.79). CONCLUSIONS: Major reductions in ischaemic burden can be achieved following CTO PCI, with more defect size reduction in patients with a larger perfusion defect, whereas hyperaemic MBF and CFR improve significantly irrespective of their baseline values or perfusion defect size. Visual summary. Major reductions in ischaemic burden can be achieved following CTO PCI. More defect size reduction in patients with a larger baseline perfusion defect. Significant hyperaemic MBF improvement irrespective of its baseline values.