BACKGROUND The optimal coronary revascularization strategy for patients with unprotected left main coronary artery (ULMCA) disease and left ventricular systolic dysfunction (LVSD) remains uncertain. The purpose of this study was to evaluate the clinical outcomes after percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) versus coronary artery bypass grafting (CABG) in patients with ULMCA disease with or without LVSD. METHODS A total of 984 patients with ULMCA disease who received a DES (n = 511) or underwent CABG (n = 473) were included in this study. We retrospectively analyzed the clinical parameters and outcomes of ULMCA disease patients with different left ventricular ejection fraction levels. RESULTS There were no significant differences in major adverse cardiac and cerebral events, all-cause death, cardiac death, myocardial infarction, or stroke between the CABG and DES groups with or without LVSD. The rate of target vessel revascularization was significantly higher with DES compared with CABG in patients without LVSD; however, the difference was not significant between the mild LVSD and severe LVSD groups. CONCLUSIONS For patients with ULMCA disease and LVSD, there was no significant difference between DES and CABG in terms of efficacy and safety. Treatment with DES was an acceptable alternative to CABG.