Purpose Platinum embolization coils produce significant CT artifacts and require multiple devices to occlude vessels. A polymer coil-plug represents an attractive alternative, offering minimal CT artifact and occlusion in a single delivery sequence. Here, we report on the short and long-term vascular occlusion capability and biocompatibility of the novel MedusaTM Vascular Plug. Materials and Methods The MedusaTM Vascular Plug (MVP) is constructed from a radiopaque polymer and is a single unit multi-coiled design. MedusaTM Vascular Plugs (EndoShape Inc., Boulder, CO) were delivered into 72 vessels in 17 acute ovine and porcine studies and in 13 arteries in 13 chronic (26 weeks) ovine studies with contralateral metal coil controls. Devices were evaluated for occlusion time in small and large arteries and veins. Extensive laboratory biocompatability testing was also conducted on the MVP. Results In the acute studies, the MedusaTM Vascular Plugs were deployed into 61 deep femoral, femoral, common femoral, and iliac arteries ranging from 4.8 to 9.4 mm diameter (mean 6.1 mm) and in 11 hypogastric, femoral, common femoral, renal, external iliac, and uterine veins from 4 to 10 mm (mean 7 mm). Vessel occlusion was confirmed in all vessels after fluoroscopic contrast injection. The MVP formed a single compact coil pack in all studies with minimal CT artifact. Arterial occlusion times ranged from 1 to 11 minutes (mean 3.8 minutes) and venous occlusion times ranged from 0.3 to 5.5 minutes (mean 2.2 minutes). In the chronic studies, vascular occlusion was compared to contra-lateral metal coil packs (Cook SST coils, Bloomington, IN) at 21 days and 1, 3, and 6 months. At the specified end points, the MedusaTM Vascular Plugs produced occlusion in 12 of 13 animals. The control coils were occluded in 5 of 13 animals. The MVP passed 15 biocompatability tests, including toxicity, mutagenicity, pyrogenicity, cytotoxicity, and hemolysis (NAMSA and Nelson Labs). Conclusion The MedusaTM Vascular Plug provides complete occlusion of a wide variety of sizes and types of blood vessels. Durable occlusion has been confirmed in long term studies. This radiopaque polymer vascular plug may offer an attractive option to platinum embolic coils.