Patients who have undergone coronary artery bypass graft (CABG) surgery are susceptible to bypass graft failure and progression of native coronary artery disease. Although the saphenous vein graft (SVG) was traditionally the most-used conduit, arterial grafts (including the left and right internal thoracic arteries and the radial artery) have improved patency rates. However, the need for secondary revascularization remains common, and percutaneous coronary intervention (PCI) has become the most common modality of secondary revascularization after CABG surgery. Procedural characteristics and clinical outcomes differ considerably from those associated with PCI in patients without previous CABG surgery, owing to altered coronary anatomy and differences in conduit pathophysiology. In particular, SVG PCI carries an increased risk of complications, and operators are shifting their focus towards embolic protection strategies and complex native-vessel interventions, increasingly using SVGs as conduits to facilitate native-vessel PCI rather than pursuing SVG PCI. In this Review, we discuss the differences in conduit pathophysiology, changes in CABG surgery techniques, and the latest evidence in terms of PCI in patients with previous CABG surgery, with a particular emphasis on safety and long-term efficacy. We explore the subject of contemporary CABG surgery and subsequent percutaneous revascularization in this complex patient population.