Background Drug eluting stents (DESs) made with biodegradable polymer have been developed in an attempt to improve clinical outcomes. However, the impact of biodegradable polymers on clinical events and stent thrombosis (ST) remains controversial. Methods We searched Medline, the Cochrane Library and other internet sources, without language or date restrictions for articles comparing clinical outcomes between biodegradable polymer DES and durable polymer DES. Safety endpoints were ST (definite, definite/probable), mortality, and myocardial infarction (MI). Efficacy endpoints were major adverse cardiac event (MACE) and target lesion revascularization (TLR). Results We identified 15 randomized controlled trials (n=17 068) with a weighted mean follow-up of 20.6 months. There was no statistical difference in the incidence of definite/probable ST between durable polymer- and biodegradable polymer-DES; relative risk (RR) 0.83; 95% confidence interval (CI) 0.62-1.11; P=0.22. Biodegradable polymer DES had similar rates of definite ST (RR 0.94, 95% CI 0.66-1.33, P=0.72), mortality (RR 0.94, 95% CI 0.82-1.09, P=0.43), MI (RR 1.08, 95% CI 0.92-1.26. P=0.35), MACE (RR 0.99, 95% CI 0.91-1.09, P=0.85), and TLR (RR, 0.94, 95% CI 0.83-1.06, P=0.30) compared with durable polymer DES. Based on the stratified analysis of the included trials, the treatment effect on definite ST was different at different follow-up times: year favoring durable polymer DES and >1 year favoring biodegradable polymer DES. Conclusions Biodegradable polymer DES has similar safety and efficacy for treating patients with coronary artery disease compared with durable polymer DES. Further data with longer term follow-up are warranted to confirm the potential benefits of biodegradable polymer DES.