Tunable biodegradable polyurethanes (PUs) with favorable mechanical properties were synthesized from 1,6-hexamelthylene diisocyanate (HDI) as the hard segment, poly(E-caprolactone) (PCL) as the soft segment, and L-cystine ester as chain extender. The structure of PUs was confirmed by FTIR and 1H-NMR. The results of differential scanning calorimeter, thermogravimetric analysis, dynamic mechanical analysis, and tensile test revealed that the thermal and mechanical properties of PUs were strongly influenced by the molecular weight of soft segment PCL. In the presence of glutathione, the disulfide group cleaved into thiols, realizing the PUs degraded and the molecular weight decreased. For PU [550], it remained only 50% of the original Mw. Evaluation of cell viability demonstrated the nontoxicity of the PUs, which facilitated their potential in biomedical applications. (c) 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013