Aims Recent concerns have emerged on the potential higher risk of stent thrombosis after Drug-eluting stents (DES) implantation, that might be even more pronounced among ST-segment elevation myocardial infarction (STEMI) patients. The aim of the current study was to evaluate, by a meta-analytic approach, whether the benefits and safety of DES as compared to bare-metal stents (BMS) in patients undergoing primary angioplasty for STEMI may be influenced by the duration of prescription of dual oral antiplatelet therapy. Methods The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL). We examined all completed randomized trials of DES for STEMI. The following key words were used for study selection: randomized trial, myocardial infarction, reperfusion, primary angioplasty, stenting, DES, sirolimus-eluting stent (SES), Cypher, paclitaxel-eluting stent (PES), Taxus. Information on study design, type of stent, inclusion and exclusion criteria, primary endpoint, number of patients, angiographic and clinical outcome, were extracted by two investigators. Disagreements were resolved by consensus. Results A total of 12 trials were included in the meta-analysis, involving 4,351 patients (2,260 or 51.9% randomized to DES and 2,091 or 48.1% randomized to BMS). In five trials (involving 1690 patients) dual oral antiplatelet therapy was prescribed for at least 1 year. The outcome of DES as compared to BMS was not affected by the duration of dual antiplatelet therapy in terms of death (P interaction = 0.16), reinfarction (P interaction = 0.91) and in-stent thrombosis (P interaction = 0.26) and TVR (P interaction = 0.38). These data were confirmed by the use of a meta-regression analysis. Conclusions This meta-analysis shows that among selected STEMI patients undergoing primary angioplasty, DES (SES and PES), as compared to BMS, are safe and their benefits are not affected by the duration of clopidogrel prescription.