New biodegradable poly(ester urethane)/soy protein isolate (PEU/SPI) hybrids were prepared by in situ polymerization. The chemical incorporation of the SPI into the backbone chain of the PEU was facilitated by the reaction of the amine functional groups of SPI with methylene diphenyl diisocyanate (MDI). X-ray diffraction results showed that the chemical incorporation of SPI into PEU significantly changed the molecular structure of the PEU. The PEU/SPI hybrids exhibited higher thermal decomposition temperature and significant increase in the modulus compared with that of pure PEU. Microscopic examination of the morphology of PEU/SPI hybrids confirmed very fine and homogeneous SPI dispersion in PEU. The hydrolytic degradation of the PEU in a phosphate buffer solution was accelerated by incorporation of SPI, which was confirmed by water absorption and scanning electron microscopy of the samples after up to 10 weeks immersion in the buffer solution. This study provides a facile and innovative method of controlling the biodegradation rate of pure PEU with the additional advantage of environmentally-benign biodegradation of the hybrid PEU/SPI polymer, making the concept potentially widely applicable. Published by Elsevier Ltd.