Background: Percutaneous coronary intervention (PCI) is common in patients with prior coronary artery bypass graft surgery (CABG), however, there is limited data on the association between the PCI target-vessel and clinical outcomes. In this article, we provide a state-of-the-art overview of the contemporary management of patients with prior CABG and a clear indication for revascularization. Methods: We performed a structured literature search of PubMed and Cochrane Library databases from inception to March 2021. Relevant studies were extracted and synthesized for narrative review. Results: Twenty-six observational studies focusing on PCI of bypass graft versus native coronary artery lesions in 366,060 patients with prior CABG were included. The data from observational studies suggest that bypass graft PCI is associated with higher short- and long-term major adverse cardiac events compared to native coronary artery PCI. Conclusions: Whenever feasible, native coronary artery PCI should be the prioritized treatment for saphenous vein graft failure. Prospective randomized trials are needed to elucidate the optimal revascularization strategy for patients with prior CABG.