The relative safety and efficacy of percutaneous coronary intervention (PCI) with drug-eluting stent (DES) and coronary artery bypass grafting (CABG) in patients with left ventricular (LV) systolic dysfunction remains controversial; therefore we conducted this meta-analysis to identify the optimal strategy for such cohorts. A comprehensive search of the electronic databases including PubMed, EMBASE, and Cochrane Library from January 1, 2003 to March 1, 2018 was performed to identify the eligible adjusted observational studies. The primary end point was all-cause death during the longest follow-up, and the generic inverse variance random-effect model was used to estimate the pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Eight adjusted observational studies involving 10,268 patients were included. Compared with CABG, PCI with DES was associated with higher risk of all-cause mortality (HR 1.36, 95% CI 1.16 to 1.60), cardiac mortality (HR 2.20, 95% CI 1.63 to 2.95), myocardial infarction (HR 1.69, 95% CI 1.28 to 2.24), and repeat revascularization (HR 4.95, 95% CI 3.28 to 7.46) in patients with coronary artery disease and LV systolic dysfunction. Besides, separate analysis of patients with LV ejection fraction <35% or left main and/or multivessel disease obtained similar results compared with the overall analysis. However, DES and CABG shared similar rates of stroke (HR 0.92, 95% CI 0.67 to 1.26). In conclusion, CABG appears to be superior to PCI with DES for patients with coronary artery disease and LV systolic dysfunction, particularly in patients with severe LV systolic dysfunction or those with left main and/or multivessel disease.