Background:  There is only limited information about cost-effectiveness of drug-eluting compared with bare metal stents (BMS) over a time horizon of more than 1 year.Methods and Results:  We developed a Markov model based on clinical outcome data from a meta-analysis including 17 randomized controlled trials comparing drug-eluting versus BMS with a minimum follow-up of 1 (n = 8221) and a maximum follow-up of 3 years (n = 4105) in patients with chronic coronary artery disease. Costs were obtained as reimbursement rates for diagnosis related groups from the US Centers for Medicare and Medicaid Services. All costs and effects were discounted at 3% annually. All costs are reported in US dollars of the financial year 2007. The incremental effects are 0.002 (95% confidence interval −0.039 to 0.041) quality-adjusted life-years (QALYs) for the sirolimus- and −0.001 (−0.040 to 0.038) QALYs for the paclitaxel-eluting stents (PES). The incremental costs are $2790 for the sirolimus- and $3838 for the PES. The incremental cost-effectiveness ratio is >$1,000,000 per QALY for the sirolimus-eluting stent. PES are dominated by BMS (i.e., less effective and more costly). Among various sensitivity analyses performed, the model proved to be robust.Conclusions:  Our analysis from a US Medicare perspective suggests that drug-eluting stents are not cost-effective compared with BMS when implanted in unselected patients with symptomatic ischemic coronary artery disease.