BACKGROUND There are limited data regarding the long-term prognosis of percutaneous coronary intervention treatment for left main (LM) ostial stenosis. OBJECTIVE The present study sought to investigate the long-term clinical outcomes and risk factors for adverse events in LM ostial lesions following drug-eluting stent implantation (DES) in a large cohort of an LM registry database. METHODS Patients presenting with LM coronary disease from January 2004 to December 2016 at Fuwai Hospital were included. The primary endpoint was target vessel failure (TVF), a composite endpoint of cardiac death, target vessel myocardial infarction and target vessel revascularisation. Cox proportional hazards models were constructed to identify independent predictors. RESULTS Among 4,625 LM patients, 627 (13.6%) patients were identified with LM ostial lesions. There were more female patients in the ostial group (31.3%), compared with the shaft (18.1%) and bifurcation groups (19.9%) (p<0.0001). Among patients with DES implantation, 3-year TVF occurred in 44 patients (7.5%) in the ostial group, which is comparable with the other two groups. Myocardial infarction (MI) was significantly lower in the ostial group (2.0%) compared with the bifurcation group (4.2%) (p=0.02), especially for MI events originating in the LM vessel (p=0.02). For patients with ostial LM disease who received percutaneous coronary intervention (PCI) treatment, procedural complications were an independent risk factor for long-term cardiac death or MI, while a more recent PCI proved to be a protective factor. CONCLUSIONS PCI treatment for ostial LM lesions achieved favourable long-term outcomes, with a similar MI risk compared with the mid-shaft group but a significantly lower risk of MI compared with the distal group.