The aim of this study was to compare the clinical and hemodynamic outcomes of plain vs paclitaxel-coated percutaneous transluminal angioplasty (PTA) in patients with infrainguinal vein bypass stenosis. A single-center retrospective analysis was conducted of consecutive patients treated by infrainguinal bypass PTA. Primary study end points were primary and assisted primary patency. Secondary end points were clinical and hemodynamic improvement, limb salvage, and survival. Society for Vascular Surgery reporting standards were applied. From April 2008 to November 2014, 83 infrainguinal vein bypasses were treated for graft stenosis by plain (group A, n = 41) or by paclitaxel-coated PTA (group B, n = 42). The groups did not differ significantly in mean age (71.9 years for both groups; P = .99), hypertension (P = 1.0), hyperlipidemia (P = .5), diabetes (P = .6), coronary artery disease (P = 1.0), smoking (P = 1.0), preoperative ankle-brachial index (P = .08), or bypass characteristics (below-knee, P = .82). Technical success rate was 100% for both groups. Mean follow-up was 2.9 years for group A patients and 2.2 years for group B patients (P = .08). No patient was lost to follow-up. Primary patency rates were 88% vs 87% and 73% vs 75% (P = .19) and assisted primary patency rates were 88% vs 90% and 77% vs 84% (P = .76) for group A and B patients at 1 and 2 years, respectively. Repeat target lesion revascularization rates were 22% vs 14% (P = .17). At the last follow-up, there were eight vs seven bypass occlusions (P = .74) for group A and B patients, respectively. In univariate analysis, proximal in-graft stenosis (Cox F, P = .041), bypass failure <6 months after bypass surgery (Cox F, P = .013), more than one bypass stenosis per graft (Cox F, P = .047), and redo bypass procedure (Cox F, P = .0001) were significantly related to assisted primary bypass patency. Immediate hemodynamic and sustained clinical improvement rates were 88% vs 86% and 70% vs 73% for group A and B patients, respectively. There were three vs one major amputations (P = .36) and eight vs seven deaths (P = .78) in group A and B patients, respectively. Paclitaxel-coated and plain angioplasty of significant infrainguinal vein bypass stenoses performed equally well in clinical and hemodynamic improvement and in primary and assisted primary bypass patency rates.