Background: The short- and mid-term outcomes of the second-generation cobalt-chromium sirolimuseluting stent (CoCr-SES) in real-world patients had been reported previously, but the long-term performance remained unclear. The objective of this analysis was to evaluate the long-term safety and efficacy of the second-generation CoCr-SES from the FOCUS registry. Methods: The FOCUS registry (ClinicalTrials.gov Identifier: NCT00868829) enrolled all-comers eligible to receive Firebird-2 CoCr-SES. Follow-up was continued to 3 years to evaluate long-term safety and effectiveness of the second-generation CoCr-SES in real-world practice. Results of the extended-use group and standard-use group are compared to explore performance of CoCr-SES in more severe patients with more complex lesions. Results: The rate of 3-year MACE was 7.37%, consisting of 84 cases (1.78%) of cardiac death, 166 cases (3.52%) of MI and 98 cases (2.08%) of TVR. ARC definite/probable stent thrombosis happened in 34 (0.72%) patients, only 3 new cases (< 0.1%) of very late stent thrombosis was reported in the third year. Meanwhile, the difference of MACE (7.77% vs. 6.06%; P=0.058), TLF (4.71% vs. 3.49%; P=0.085) and ARC definite/probable stent thrombosis (0.83% vs. 0.37%; P=0.116) between extended-use group and standard-use group showed no significance. Conclusions: The second-generation CoCr-SES was associated with continued low rates of 3-year MACE, TLF and stent thrombosis in a broad spectrum of patients. © Journal of Thoracic Disease.