BACKGROUND AND OBJECTIVES: The drug-eluting balloon (DEB) catheter system was developed to treat restenosis. Furthermore, DEB angioplasty has been shown to reduce restenosis risk when compared to drug-eluting stents (DES) in patients with in-stent restenosis (ISR) or small vessel disease (SVD). In addition, DEB angioplasty reduces costs due to fewer revascularizations and reduced clopidogrel treatment length. The objective of this study was to predict the expected cost-savings when DEB is substituted for DES in patients with ISR or SVD. SUBJECTS AND METHODS: The subjects included were patients treated by DES at Seoul National University Hospital from January 2006 to June 2009, with clinical data after percutaneous coronary intervention, were. A model was developed to allow the costs of DES and the calculated costs of DEB incurred by patients with ISR or SVD to be compared. The overall cost of DEB was calculated to be 1,256,150 won and the overall cost of DES was 2,102,500 won, and the cost of clopidogrel was 2,168 won. Expected repeat revascularizations within 12 months of DEB were calculated based on information provided by the Paclitaxel-Eluting PTCA-Balloon Catheter in Coronary Artery (PEPCAD) I and II trials. RESULTS: By substituting DEB for DES, total cost (including the cost of initial DEB treatment, the cost of repeat revascularization after DEB treatment, and the cost of clopidogrel treatment) was found to be 34% lower in ISR patients and 48% lower in SVD patients. CONCLUSION: DEB angioplasty will significantly reduce costs as compared to DES in ISR and in SVD patients.