Background Heart failure might be an important determinant in choosing coronary revascularization modalities. There was no previous study evaluating the effect of heart failure on long‐term clinical outcomes after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG). Methods and Results Among 14 867 consecutive patients undergoing first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013 in the CREDO‐Kyoto PCI/CABG registry Cohort‐3, we identified the current study population of 3380 patients with three‐vessel or left main coronary artery disease, and compared clinical outcomes between PCI and CABG stratified by the subgroup based on the status of heart failure. There were 827 patients with heart failure (PCI: N=511, and CABG: N=316), and 2553 patients without heart failure (PCI: N=1619, and CABG: N=934). In patients with heart failure, the PCI group compared with the CABG group more often had advanced age, severe frailty, acute and severe heart failure, and elevated inflammatory markers. During a median 5.9 years of follow‐up, there was a significant interaction between heart failure and the mortality risk of PCI relative to CABG (interaction P =0.009), with excess mortality risk of PCI relative to CABG in patients with heart failure (HR, 1.75; 95% CI, 1.28–2.42; P <0.001) and no excess mortality risk in patients without heart failure (HR, 1.04; 95% CI, 0.80–1.34; P =0.77). Conclusions There was a significant interaction between heart failure and the mortality risk of PCI relative to CABG with excess risk in patients with heart failure and neutral risk in patients without heart failure.