OBJECTIVES: Drug-eluting stents (DES) and bare-metal stents (BMS) are both used widely in percutaneous coronary interventions (PCI). However, the incremental cost-effectiveness of DES versus BMS varies considerably between studies. A systematic review is performed to gain insight how modeling influences the cost-effectiveness of DES versus BMS. METHODS: We reviewed modeling studies published until February 2011 that studied the cost-effectiveness of DES versus BMS. We then extracted various parameters (e.g., model type, time horizon, data sources, choice of disease states) and explored the influence of these parameters on the cost-effectiveness outcomes. RESULTS: The incremental cost-effectiveness ratios (ICER) from the 22 eligible studies ranged from DES being dominated by BMS to DES being dominant. Different parameters can contribute to these differences, including time horizon, assumptions concerning stent efficacy, study perspective, stent cost prices and the specific type of stents being compared. Almost half of the studies used a time horizon ≤12 months, assuming that differences in clinical events between the two stents occur in the first year. However, published literature contradicts this assumption since DES can induce very late in-stent thrombosis. Moreover, many studies base restenosis rates on angiographic follow-up. Since angiography overestimates the difference in restenosis rate between DES and BMS, its use leads to an overestimate of quality-adjusted life-years gained and number of avoided reinterventions and an underestimate of the costs of the DES strategy. The price premium of DES versus BMS differs considerably between studies (€900- €3300) and this difference also affects the ICER. CONCLUSIONS: Choices made in cost-effectiveness models to compare DES with BMS lead to wide variation in cost-effectiveness estimates, making it difficult to conclude that DES is more cost-effective than BMS. Since 80,000 PCIs are performed per year in the UK, it is very important to obtain valid estimates of the cost-effectiveness of DES versus BMS.