Endovascular deployment of drug-coated balloons (DCB) is an emerging strategy for the revascularization of arterial disease. Randomized clinical trials have demonstrated DCB effectiveness, but a recent meta-analysis reported increased mortality risk in humans with use of DCBs containing the common antiproliferative drug paclitaxel. While many factors could have contributed to adverse outcomes, current DCB designs have poor drug delivery efficiency, risk of systemic toxicity, and limited potential to retain therapeutic drug concentrations within the arterial wall following the procedure. Our study focuses on developing a strategy to enhance acute drug transfer from the balloon to the arterial wall over the short procedural window (∼30-120 s). We employed ultraviolet-ozone plasma (UVO) treatment to increase the hydrophilicity of a prototypical balloon material (Nylon-12) and subsequently applied a urea-paclitaxel coating previously shown to undergo favorable adhesive interactions with the arterial wall under simulated ex-vivo deployment. A series of assays were performed to characterize our experimental DCBs in terms of UVO-induced alterations in balloon surface hydrophobicity, formed coating microstructure, coating stability, and acute drug transfer to the arterial wall. Obtained results suggest that the UVO-based surface modification of angioplasty balloons is a promising design strategy and highlights the critical role of coating microstructure in determining the drug transfer efficiency in DCB therapy.