Everolimus-eluting stents are largely used for left main (LM) percutaneous coronary interventions (PCI). Long-term follow-up of patients who underwent LM PCI in a real world clinical setting, in particular women, have been scarcely reported. Consecutive patients who underwent unprotected LM PCI with EES at a single Institution from December 2006 to April 2016 were included. Main outcome assessed was the occurrence of major adverse cardiovascular events (MACE) as a composite of death, myocardial infarction or target lesion revascularization at follow-up. Overall, 589 patients (20.8% women) were included in the present analysis. Women were older, had lower body mass index and more frequently hypertensive compared with men. Main clinical presentation was stable coronary artery disease (CAD); unstable angina was more frequently observed in women compared with men, whereas ST-elevation myocardial infarction was less frequent. After 69.7 ± 28.3 months of follow-up, 47 patients overall experienced MACE (1.43 per 100*patients/year). MACE rate was higher in women compared with male patients, with a rate of 2.49 and 1.17 per 100*patients/year, respectively (p = 0.015). The difference was driven mainly by higher mortality in women (0.89 vs 0.15 per 100*patients/years, p = 0.002). At multivariable Cox regression, female gender was independently associated with an increased risk of MACE at follow-up (hazard ratio 2.21, 95% confidence interval 1.20 to 4.08, p = 0.011). In conclusion, EES can be safely and effectively adopted for LM PCI.