Abstract Objectives The aim of this study was to investigate the hypothesis that a novel biodegradable polymer–coated, cobalt-chromium (CoCr), sirolimus-eluting stent (BP-SES) is noninferior in safety and efficacy outcomes compared with a durable polymer (DP)-SES. Background No randomized trials have the compared safety and efficacy of BP-SES versus DP-SES on similar CoCr platforms, thereby isolating the effect of the polymer type. Methods In this prospective, single-blind, randomized trial conducted at 32 Chinese sites, 2,737 patients eligible for coronary stenting were treated with BP- or DP-SES in a 2:1 ratio. The primary endpoint was 12-month target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, or clinically indicated target lesion revascularization. Secondary endpoints included TLF components, and definite/probable stent thrombosis. Results At 12 months, the difference in the primary endpoint of TLF between BP-SES (6.3%) and DP-SES (6.1%) groups was 0.25% (95% confidence interval: −1.67% to 2.17%, p for noninferiority = 0.0002), demonstrating noninferiority of BP-SES to DP-SES. Individual TLF components of cardiac death (0.7% vs. 0.6%, p = 0.62), target vessel myocardial infarction (3.6% vs. 4.3%, p = 0.39), and clinically indicated target lesion revascularization (2.6% vs. 2.2%, p = 0.50) were similar, as were low definite/probable stent thrombosis rates (0.4% vs. 0.6%, p = 0.55). Conclusions In this large-scale real-world trial, BP-SES was noninferior to DP-SES for 1-year TLF. (Evaluate Safety and Effectiveness of the Tivoli ® DES and the Firebird ® DES for Treatment of Coronary Revascularization; NCT01681381 )