This study aimed to evaluate the association between percutaneous coronary intervention (PCI) treatment and all-cause mortality in patients with ischemic heart failure with left ventricular systolic dysfunction and functional mitral regurgitation (FMR). We included 1,483 patients of which 39.5% (n = 586) had moderate-to-severe FMR. Multivariable Cox proportional hazard model was used to assess the association between PCI treatment and all-cause mortality. Furthermore, propensity score matching was used to account for non-random treatment assignment. In those with none-to-mild FMR, after a median follow-up of 3.1 years, the cumulative rate of all-cause mortality between the PCI and non-PCI groups was comparable (10.1% vs 14.2%), with an adjusted hazard ratio (HR) of 0.731 (95% confidence interval [CI] 0.438 to 1.221, p = 0.232). In those with moderate-to-severe FMR, after a median follow-up of 2.9 years, the cumulative rate of all-cause mortality was lower in the PCI group (20.4% vs 31.6%), with an adjusted HR of 0.660 (95% CI 0.469 to 0.929, p = 0.017). The result was confirmed with propensity matching (HR 0.596 and 95% CI 0.363 to 0.977, p = 0.038). The mortality benefit associated with PCI treatment in patients with moderate-to-severe FMR was consistent regardless of the age, gender, reason for admission, presence of diabetes mellitus, left ventricular ejection fraction value, left main and 3-vessels disease. In conclusion, in patients with ischemic heart failure with left ventricular systolic dysfunction and moderate-to-severe FMR, PCI treatment was associated with improvement in all-cause mortality. Randomized clinical trials are needed to confirm the current results. (C) 2022 Elsevier Inc. All rights reserved.