The release rate of heparin from monolithic devices composed of raffinose, β-cyclodextrin, polyethylene oxide (Mw 20,000, PEO), and hydrophobic polyether urethane (biomer) was investigated. Water soluble raffinse, β-cyclodextrin, and PEO blended into the biomer provided a controlled release of heparin. The release rate of heparin could be controlled by the content of raffinose, β-cyclodextrin, and PEO in the devices. The mechanism of release rate increased by the raffinose, β-cyclodextrin, and PEO may result from the formation of channels and pores in the biomer matrices following the swelling and the change in the physical structure of polymer net work. Hydrophobic polyurethane containing raffinose, β-cyclodextrin, and PEO can provide a hydrophilic antithrombogenic material for prolonged release of heparin.