Over the past decade, the advent of drug-eluting stents (DES) has revolutionised the field of interventional cardiology by having a major impact on patient care through their efficacy in reducing the need for repeat revascularisation. A number of stents capable of delivering an anti-proliferative agent designed to prevent neointimal hyperplasia, the principal mechanism of restenosis after stenting, have been evaluated; four of these devices are currently approved by the U.S. Food and Drug Administration (FDA). Bare metal stent (BMS) and first-generation DES, such as sirolimus-eluting (SES-Cypher(®)) and paclitaxel-eluting stents (PES-Taxus(®)), have further improved results of percutaneous coronary intervention (PCI) by improving early results and reducing the risk of restenosis. However, there is currently debate on the safety of these first-generation DES, given the potential for late stent thrombosis (LST), especially after discontinuation of dual anti-platelet therapy. Second-generation DES, such as zotarolimus-eluting (ZES-Endeavor(®)) and everolimus-eluting stents (EES-Xience V(®)), are become available in the USA and/or Europe. Recently, long-term results comparing DES with BMS in patients with ST-segment-elevation MI (STEMI) have raised some questions about the long-term risks of the drug-eluting devices. It may be useful to pause, reflect for a moment, and consider some recent pertinent results regarding their wider use. This systematic review tries to provide a concise and critical appraisal of the data available to compare first and second generation stents especially to assess risk of stent thrombosis (ST) with second-generation DES.