OBJECTIVE: Pressure-based fractional flow reserve (FFR) is an invasive test for assessing the functional significance of intermediate coronary stenoses. Previous studies have found that FFR testing to guide percutaneous coronary intervention (PCI) is cost-effective. In this study we evaluate the impact of using drug-eluting stents (DES) on this decision. METHODS: We developed a Markov model to compare the long-term costs and outcomes of 2 strategies for patients with indeterminate coronary stenosis scheduled for PCI: 1) Universal PCI (UNIV) without FFR testing, and 2) FFR testing followed by PCI only for those with FFR<0.75 (TEST). Base-case: 60-year-old man under the optimistic assumption (for UNIV) that relative mortality reduction with revascularization is independent of functional significance. Data: long-term clinical outcomes of PCI and medical management including recurrence rates, disease progression, and quality of life based on published literature. Based on fixed effects meta-analysis, we estimated that DES reduce clinical restenosis rates by 79% compared with bare metal stents (BMS). Perspective: societal. Discounting: 3% per year. RESULTS: For the case of BMS, UNIV increased costs by $2800/patient and improved outcome by 12 quality-adjusted life days (QALD), yielding an incremental cost-effectiveness ratio (ICER) of $84,000 per quality-adjusted life year (QALY) gained. When considering the benefits of DES, incremental costs increased to $3300 and benefit of UNIV increased to 18 QALDs, with an ICER of $69,000/QALY. Results were similar for women and over a broad age range (55-75 years). If we assumed that PCI in functionally insignificant stenoses did not reduce long-term mortality, the ICER for UNIV vs. TEST was > $1 million/QALY. CONCLUSIONS: Regardless of stent type (BMS or DES), measuring FFR to guide the decision to perform PCI leads to significant cost savings. Even under very optimistic assumptions regarding mortality benefits and restenosis rates for DES, universal stenting does not appear to be cost-effective when compared to other well-accepted interventions in health care.