Objectives The purpose of this study was to investigate whether fractional flow reserve (FFR) should be performed for patients with coronary artery disease (CAD) to guide the percutaneous coronary intervention (PCI) strategy. Background PCI is the most effective method to improve the outcomes of CAD. However, the proper usage of PCI has not been achieved in clinical practice. Methods A meta-analysis was performed on angiography-guided PCI and FFR-guided PCI strategies. Prospective and retrospective studies were included when research subjects were patients with CAD undergoing PCI. The primary endpoint was the rate of major adverse cardiac events (MACE) or major adverse cardiac and cerebrovascular events (MACCE). Secondary endpoints included death, myocardial infarction (MI), repeat revascularisation and death or MI. Results Four prospective and three retrospective studies involving 49 517 patients were included. Absolute risks of MACE/MACCE, death, MI, revascularisation and death or MI for angiography-guided PCI and FFR-guided PCI were 34.8% vs 22.5%, 15.3% vs 7.6%, 8.1% vs 4.2%, 20.4% vs 14.8%, and 21.9% vs 11.8%, respectively. The meta-analysis demonstrated that FFR-guided PCI was associated with lower MACE/MACCE (OR: 1.71, 95% CI 1.31 to 2.23), death (OR: 1.64, 95% CI 1.37 to 1.96), MI (OR: 2.05, 95% CI 1.61 to 2.60), repeat revascularisation (OR: 1.25, 95% CI 1.09 to 1.44), and death or MI (OR: 1.84, 95% CI 1.58 to 2.15) than angiography-guided PCI strategy. Conclusions This meta-analysis supports current guidelines advising the FFR-guided PCI strategy for CAD. PCI should only be performed when haemodynamic significance is found.