Introduction: The salutary effect of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has been questioned. The aim of this study was to assess the effects of CTO PCI on absolute myocardial blood flow (MBF), as compared with PCI of non-occlusive lesions (stenosis >90% or fractional flow reserve-guided (≤0.80)).Methods: Consecutive patients with a preserved left ventricular function and a clinically indicated successful PCI were considered eligible for inclusion if oxygen labeled H2(15)O water positron emission tomography (PET) was performed prior and after PCI. Baseline, follow-up and change of absolute (stress) MBF and coronary flow reserve (CFR) were compared between patients with CTO and significant non-occlusive lesions.Results: Sixty-five (34 CTOs vs. 31 non-occlusive lesions) patients were included for analysis. Baseline stress MBF of the myocardial CTO area was significantly lower compared with the myocardial area of non-occlusive lesions (1.29±0.40 vs. 1.59±0.59 mL·min·g, p=0.02), whilst baseline CFR was not (1.62±1.01 vs. 1.92±0.74, p=0.19). Vessel specific stress MBF and CFR improved significantly between baseline and follow-up in patients treated with PCI for CTO as well as non-occlusive lesions (stress MBF: CTO: 1.29±0.40 to 2.62±0.75 mL·min·g, p<0.001 and non-CTO: 1.59±0.59 to 2.86±0.96 mL·min·g, p<0.001; CFR: CTO: 1.62±1.01 to 3.23±1.16, p<0.001 and non-CTO: 1.92±0.74 to 3.00±0.81, p<0.001). There were no significant differences between CTO- and non-CTO patients in quantitative improvement of stress MBF (Δ1.34±0.61 vs. Δ1.27±1.08 mL·min·g, p=0.76) and stress MBF at follow-up (2.62±0.75 vs. 2.86±0.96 mL·min·g, p=0.27). CFR at follow-up (3.23±1.16 vs. 3.01±0.80, p=0.38) was comparable between CTO- and non-CTO patients, however, CFR improvement showed a trend toward a bigger increase in patients treated for a CTO (Δ1.61±1.24 vs. 1.08±1.02, p=0.07).Conclusions: The effect of PCI on stress MBF and CFR between patients treated for CTO and significant non-occlusive lesions is comparable. Baseline stress MBF in a myocardial CTO area is significantly lower compared to the myocardial area of non-occlusive lesions. However, PCI resulted in comparable stress MBF values at follow-up.