OBJECTIVES: To evaluate the cost-effectiveness of serolimus-eluting stents (SES) to bare-metal stents (BMS) in patients with single-vessel coronary artery disease (SVD) compared with patients with multi-vessel disease (MVD). METHODS: In the prospective GERSHWIN study in 35 hospitals in Germany, patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) were electively treated with SES or BMS (sequential control design). Standardized questionnaires completed by patients and physicians through 18 months following PCI documented major adverse coronary events (MACE), including death, myocardial infarction, coronary artery bypass surgery and re-PCI in target vessel, as well as disease-related direct and indirect costs. RESULTS: From April 2003 until June 2005, 658 patients were treated with SES (87% male, mean age 63±9) und 294 patients with BMS (79% male, mean age 64±10). SVD was documented in 34% BMS patients and 29% SES patients. After 18 months, 8% of SES and 25% of BMS patients with SVD had suffered MACE in comparison to 15% of SES and 19% of BMS patients with MVD, indicating a difference in the effect of SES with respect to the underlying CAD status (p adjusted= 0,023). In SVD, SES and BMS incurred total costs of EUR 11,832 and 12,399, respectively. In MVD, SES and BMS incurred total costs of EUR 14,964 and 12,026, respectively (p adjusted=0,003). In patients with SVD, the cost-effectiveness of SES was EUR 12,805 per patient free from MACE compared to EUR 16,488 in BMS. In patients with MVD, the cost-effectiveness of SES was EUR 17,522 per patient free from MACE compared to EUR 14,810 in BMS. CONCLUSION: In patients with SVD, SES is more cost effective than BMS whereas in patients with MVD, SES is less cost effective than BMS.