Percutaneous coronary interventions for the treatment of coronary artery disease have evolved substantially, from plain balloon angioplasty to drug-eluting stents (DES). Although DES have significantly reduced restenosis rates, mid- and long-term complications such as in-stent restenosis (ISR), stent thrombosis, and the need for prolonged dual antiplatelet therapy remain clinically relevant. In this context, drug-coated balloons (DCB) have emerged as an alternative revascularization strategy designed to deliver antiproliferative drugs locally without leaving a permanent intravascular implant.

DCBs transfer antiproliferative agents—most commonly paclitaxel and, more recently, sirolimus—directly into the vessel wall during balloon inflation, thereby inhibiting neointimal hyperplasia. This “leave nothing behind” concept aims to promote more physiological vascular healing while minimizing late complications associated with permanent metallic scaffolds and reducing long-term antiplatelet therapy requirements. Robust clinical evidence supports the use of DCBs as a first-line therapy for ISR, demonstrating superiority over plain balloon angioplasty and efficacy and safety comparable to repeat DES implantation. Long-term follow-up data extending up to ten years indicate that, when applied with appropriate lesion preparation and patient selection, DCB-based strategies provide durable clinical outcomes.

Beyond ISR, DCBs are increasingly investigated in de novo coronary lesions, small-vessel disease, bifurcation lesions, diffuse long lesions, and in patients at high bleeding risk. These settings highlight the potential advantages of avoiding additional metal layers and preserving future treatment options. Nevertheless, evidence remains limited for certain indications, particularly large-vessel de novo lesions and highly complex coronary anatomies. Further large-scale, randomized trials with standardized procedural protocols and long-term follow-up are required to clearly define the role of DCBs across broader clinical scenarios. This review summarizes the mechanisms of action, clinical evidence, safety considerations, and future perspectives of DCB technology in contemporary coronary interventions.