AbstractBiobased 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.