Introduction: Open vascular reconstructions (OVR), such as bypass grafts and dialysis access, are commonly performed to treat cardiovascular and renal diseases. Unfortunately, OVR often fail, largely due to intimal hyperplasia (IH), and there are no clinical methods to prevent the failure. OVR provide accessibility to the graft surface, hence an opportunity for perivascular drug delivery to suppress IH. However, drug release generally lasts for limited time whereas long-term efficacy is important for clinical success. Goals: We addressed a prominent question in clinical translation: can IH suppression be realistically sustained for a long term (longer than 6 months) via shorter-term perivascular interventions? Methods: We applied Pericelle, a nanoparticle+hydrogel system for perivascular delivery of the IH-mitigating drug rapamycin, to a modified rat vein-graft model that exhibits long-term IH progression. Results: IH was reduced throughout 3, 6, and 9 months, as indicated by morphometry (115.58±27.89 to 40.34±5.18 at 9 months) and ultrasonography (Fig 1), although rapamycin release was estimated to be around 3 months. Pericelle also mitigated IH in porcine arteriovenous fistulas (Fig 2). Conclusions: Suppression of vein-graft IH can be sustained much beyond drug release; Pericelle provides a potential strategy for reducing OVR failure. We thank Dr. Keith Ozaki and Dr. Prabir Roy-Chaudhury for instructions on models.