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Objective: Radiosurgical treatment of brain arteriovenous malformations (AVMs) has the significant shortcomings of being limited to lesions smaller than 3 cm diameter and of a latency to cure of up to 3 years. Stimulation of thrombosis using vascular targeting is attractive as a possible means of overcoming these limitations. This study examined the effect of the vascular targeting strategy lipopolysaccharide (LPS) and soluble tissue factor (sTF) in an animal model of AVM treated with radiosurgery. Methods: Stereotactic radiosurgery (SRS, 20 animals) or sham radiation (12 animals) was administered to an animal model of AVM in 32 male Sprague-Dawley rats. Twenty- four hours after intervention, animals received an intravenous injection of LPS/sTF conjugate or normal saline. Animals were sacrificed at 1, 7, 30, or 90 days after treatment. Angiography was performed immediately prior to sacrifice and model AVM tissue was harvested for histological analysis to assess vessel thrombosis rates. Results: There was no systemic toxicity or intravascular thrombosis remote from the target region in any of the animals. SRS combined with saline resulted in thrombosis of 12% of small AVM vessels (diameter < 200μm). Thrombosis occurred in 58% of small vessels in animals that received SRS and LPS/sTF. An intermediate thrombosis rate of 43% was observed in animals given the LPS/sTF agent but no radiation. Conclusion: This study demonstrated that vascular targeting can increase intravascular thrombosis after radiosurgery and that the vessel occlusion is selective and durable.