BackgroundLong‐term clinical data on biodegradable‐polymer (BP) drug‐eluting stents (DES) are limited. The objective of this study was to assess the long‐term safety and efficacy of the BP‐DES SYNERGY compared to XIENCE V, a durable‐polymer (DP)‐DES.MethodsWe compared patients treated with BP‐DES or DP‐DES at our center from 2008 to 2020. The primary outcome was major adverse cardiac events (MACE), defined as the composite of all‐cause death, Q‐wave myocardial infarction (MI), and target vessel revascularization (TVR). Secondary endpoints were all‐cause death, Q‐wave MI, target lesion revascularization (TLR), and stent thrombosis (ST).ResultsA total of 4255 patients underwent propensity‐score matching, and 380 patients from each cohort were matched. There was no significant difference between BP‐DES and DP‐DES concerning MACE (5‐year estimates: 21.6% vs. 26.6%, log‐rank p = 0.259). Furthermore, there was no difference in the TLR rate (5‐year estimates: 7.3% vs. 8.6%, log‐rank p = 0.781). All‐cause death (5‐year estimates: 13.6% vs. 12.9%, log‐rank p = 0.72) and Q‐wave MI (5‐year estimates: 0.53% vs. 1.7%, log‐rank p = 0.427) were also comparable between the two groups. Of note, the rate of very late ST was very low and similar between the groups (5‐year estimates: 0.26% vs. 0.64%, log‐rank p = 0.698).ConclusionBP‐DES and DP‐DES demonstrate similar safety and efficacy at 5‐year follow‐up. Both can be used for the effective treatment of coronary artery disease.