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To evaluate the use of imatinib mesylate with or without bevacizumab targeting neoproliferative myofibroblast-like cells with tyrosine kinase receptor expression, as adjuncts to modern interventional therapies for the treatment of multivessel intraluminal pulmonary vein stenosis (PVS). We describe the 48- and 72-week outcomes among patients receiving imatinib mesylate with or without bevacizumab for multivessel intraluminal PVS.This single-arm, prospective, open-label US Food and Drug Administration approved trial enrolled patients with ≥2 affected pulmonary veins after surgical or catheter-based relief of obstruction between March 2009 and December 2014. Drug therapy was discontinued at 48 weeks, or after 24 weeks of stabilization, whichever occurred later.Among 48 enrolled patients, 5 had isolated PVS, 26 congenital heart disease, 5 lung disease, and 12 both. After the 72-week follow-up, 16 patients had stabilized, 27 had recurred locally without stabilization, and 5 had progressed. Stabilization was associated with the absence of lung disease (P = .03), a higher percentage of eligible drug doses received (P = .03), and was not associated with age, diagnosis, disease laterality, or number of veins involved. Survival to 72 weeks was 77% (37 of 48). Adverse events were common (n = 1489 total), but only 16 were definitely related to drug treatment, none of which were serious.Survival to 72 weeks was 77% in a referral population with multivessel intraluminal PVS undergoing multimodal treatment, including antiproliferative tyrosine kinase blockade. Toxicity specific to tyrosine kinase blockade was minimal.