INTRODUCTION AND OBJECTIVES: Long-term data after stenting of the left main coronary artery (LMCA) are scarce, especially regarding new-generation drug-eluting stents (DES). This analysis aimed to describe the 10-year clinical outcomes of patients who underwent percutaneous coronary intervention with different DES generations for LMCA disease. METHODS: Individual patient data from the randomized controlled ISAR-LEFT MAIN and ISAR-LEFT MAIN 2 trials were pooled and 10-year clinical follow-up was obtained. The Kaplan-Meier method was used to calculate event rates. The main endpoints of interest for this analysis were all-cause mortality, myocardial infarction, target lesion revascularization and definite stent thrombosis. RESULTS: A total of 1257 patients were included in this analysis, of which 650 patients were treated with new-generation DES and 607 with early-generation DES. At 10 years, the mortality rate was more than 40% in both groups. After statistical adjustment, 10-year mortality was significantly reduced in patients treated with new-generation DES compared with those treated with early-generation DES (HR CONCLUSIONS: Patients undergoing percutaneous coronary intervention for LMCA disease have high 10-year mortality regardless of DES generation. The use of new-generation DES in patients with LMCA disease is associated with improved long-term clinical outcomes compared with early-generation DES.