The efficacy and safety of polymer-free drug-eluting stents (DESs) in clinical practice is currently subject of debate; randomized trials (RCTs) conducted so far provided conflicting results or were underpowered to definitively address this question; we aimed to investigate the efficacy and safety profile of polymer-free vs. durable polymer DES by a comprehensive meta-analysis of RCTs.MEDLINE, Google Scholar, EMBASE and Cochrane databases were searched for RCTs comparing polymer-free to durable polymer DES. Safety endpoints at short-term (≤1 year) and long-term follow-up (>1-year) were: death, myocardial infarction (MI) and stent thrombosis (ST); main efficacy endpoints were: target lesion revascularization (TLR) and target vessel revascularization (TVR).Eight RCTs including 6178 patients were included. No significant differences in mortality were observed between polymer-free and durable polymer DESs at both short- and long-follow up (OR [95% CI] = 0.79 [0.58–1.08], p = 0.14; and 0.80 [0.58–1.10], p = 0.17 respectively); polymer free and durable polymer DESs provided comparable short and long-term MI rates; at short-term: OR [95% CI] = 1.13 [0.83–1.54], p = 0.44 and at long-term: OR [95% CI] = 1.27 [0.87–1.85], p = 0.22. Similarly, these two different devices proved equally effective in regards to ST, TLR and TVR over the short and long follow-up period.Polymer-free DESs are as safe and effective as durable polymer DES; however, there is no evidence of any additional benefits provided by this new technology.