Percutaneous coronary intervention (PCI) has emerged as an alternative treatment to coronary artery bypass grafting (CABG) in patients with unprotected left main coronary artery disease (ULMCAD). However, the optimal treatment for ULMCAD concomitant with chronic kidney disease (CKD) was rarely addressed. Herein, we compare the long-term outcomes of these patients treated with CABG or PCI. From January 2004 to December 2010, 185 patients with ULMCAD and CKD undergoing PCI (n = 84) or CABG (n = 101) were matched for the selection criteria. The primary end points included all-cause death, myocardial infarction (MI), stroke, repeat revascularization and major adverse cardiovascular and cerebrovascular event (MACCE). The mean age was 73.4 ± 10.3 years with male (84%) predominance. Baseline characteristics of both groups were similar, except that patients in CABG group were more frequently associated with significant stenosis of right coronary artery and triple vessel disease. Furthermore, most patients belonged to higher surgical risk population (EuroSCORE ≥ 6, PCI group: 80.9%, CABG group: 75.2%). After treatment, the 30-day mortality was 3.5% in PCI and 8.9% in CABG (P = 0.14). During the median follow-up of 3.5 years, the risk of MACCE (67% versus 55%, P = 0.048), MI (15.5% versus 6.9%, P = 0.024), and repeat revascularization (30.9% versus 7.9%, P < 0.001) was significantly higher in the PCI compared with CABG. There were no significant differences in long-term all-cause death, stroke, and impact on renal function. CABG was associated with significantly less long-term risk of MI and repeat revascularization in patients with ULMCAD and CKD.