Biobased polymeric materials are gaining increasing attention in biomedical areas. Here, we report a new class of biocompatible polyurethanes prepared from soybean oil-based polyol that was synthesized by ring-opening reaction of epoxidized monoglyceride (EMG) with lactic acid. By adjusting the molar ratio of hydroxyl to isocyanate group and the content of chain extender, soybean oil-based polyurethanes with tensile strength of 9.30-27.1 MPa and elongation at break of 74.1-110.7% were prepared, while usual lipid-based polyurethanes with the same 1,6-diisocyanatohexane as reactant hardly have tensile strength higher than 5 MPa. Mouse fibroblast cells (L-929) showed good adhesion and growth behavior on the polyurethane samples with more hydrophilic surfaces, and the cell viabilities of more than 50% were achieved with commercial tissue culture polystyrene (TCPS) disk as control. The good mechanical property and biocompatibility of the soybean oil-based polyurethanes will make them suitable for wide range of potential biomedical applications.Practical applications: The synthesized soybean oil-based polyurethanes have adjustable tensile strengths from 9.30-27.1 MPa and elongation at break of 74.1-110.7%. Along with their good biocompatibility, the polyurethanes can potentially replace wide range of part of petroleum-based polymeric materials, particularly as biomedical materials.