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Coronary artery disease (CAD) is the most common cardiovascular disorder. Vascular surgery strategies for coronary revascularization (either percutaneous or open) show a high rate of failure because of restenosis of the vessel, due to phenotypic switch of vascular smooth muscle cells (VSMCs) leading to proliferation and migration. We have previously reported that the inhibition of Kv1.3 channel function with selective blockers represents an effective strategy for the prevention of restenosis in human vessels used for coronary angioplasty procedures. However, delivery systems for controlled release of these drugs have not been investigated. Here we tested the efficacy of several formulations of elastin like recombinamers (ELRs) hydrogels to deliver the Kv1.3 blocker PAP-1 in various restenosis models. The dose and time course of PAP-1 release from ELRs click hydrogels was able to inhibit human VSMC proliferation in vitro as well as remodeling of human vessels in organ culture and restenosis in in vivo models. We conclude that this combination of active compound and advanced delivery method could improve the outcomes of vascular surgery in patients., The authors are grateful for financial support from the European Social Fund (ESF) and the European Regional Development Fund (ERDF), as well as grants from the EU H2020-NMP-2014-646075), the Spanish Ministerio de Economia y Competitividad MINECO (grants BFU2016-75360-R, DTS19/00162, MAT2016-79435-R, MAT2016-78903-R and RTI2018-096320-B-C22), the Junta de Castilla y León (grants VA114P17 and VA317P18), the CIBER-BBN, the JCyL and the Instituto de Salud Carlos III under the “Network Center of Regenerative Medicine and Cellular Therapy of Castilla and Leon”. S. Moreno-Estar and S. Serrano are predoctoral fellows of the Junta de Castilla y León and M. Arévalo-Martínez is predoctoral fellow of UVa-Santander.