Background The patients with unprotected left main coronary artery (ULMCA) stenosis and chronic total occlusion (CTO) lesions at the left anterior descending (LAD) artery are often recommended for bypass surgery. However, some of these patients are deemed inoperable or are at high risk for surgery. In this study, we explored strategies and evaluated the efficacy of percutaneous coronary intervention for the treatment of ULMCA stenosis complicated by LAD CTO. Methods From November 2001 to July 2009, 78 patients with ULMCA stenosis and LAD CTO lesions were selectively treated with stenting. Six patients (7.7%) refused surgery due to their young age (S40 years), and the other 72 patients (92.3%) were unsuitable for surgery. Reasons for poor surgical candidacy included advanced age (>80 years), chronic obstructive pulmonary, unsuitable distal target vessels for bypass, EuroSCORE ≥6, and so on. Four different strategies were applied based on the degree of left main stenosis and the ostial diameter and involvement of the left circumflex. Results Total procedural success was achieved in 94.9%, there were no deaths or thromboses. Five patients (6.4%) experienced non-Q-wave myocardial infarction in hospital. At long-term follow-up ((52±28) months), there were 3 cardiac deaths (3.8%) and 4 (5.1%) nonfatal myocardial infarctions. Angiographic follow-up was performed in 50 patients (64.1%), and target vessel revascularizations were required in 10 patients (12.8%), among which 4 nonfatal myocardial infarction patients included. The rate of major adverse cardiac events was 16.7% (13/78).Conclusions This study indicates that percutaneous intervention can be performed safely in high risk surgical patients with ULMCA and LAD CTO lesions based on individual therapeutic strategies. It may be feasible to apply this technique in selected patients mentioned above.