BACKGROUND: Physiological changes in the coronary circulation associated with percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs) remain largely unknown. This systematic review and meta-analysis aimed to investigate physiological changes in the CTO and donor vessel before and immediately after PCI, as well as at follow-up. METHODS: A comprehensive search of PubMed/MEDLINE and Embase identified relevant studies. The primary end point was the mean difference (MD) between fractional flow reserve myocardium (FFR RESULTS: A total of 17 studies were included. The myocardial blood flow in the donor vessel increased after CTO revascularization (FFR CONCLUSION: Available evidence suggests that CTO revascularization leads to an immediate and long-term improvement in blood supply to downstream myocardium, mediated in part by a favorable time-dependent shift in epicardial vessel, collateral, and microcirculatory function.