We have developed a family of synthetic biodegradable polymers that are composed of structural units endogenous to the human metabolism, designated poly(polyol sebacate) (PPS) polymers. Material properties of PPS polymers can be tuned by altering the polyol monomer and reacting stiochiometric ratio of sebacic acid. These thermoset networks exhibited tensile Young's moduli ranging from 0.37+/-0.08 to 378+/-33 MPa with maximum elongations at break from 10.90+/-1.37% to 205.16+/-55.76%, and glass transition temperatures ranging from approximately 7-46 degrees C. In vitro degradation under physiological conditions was slower than in vivo degradation rates observed for some PPS polymers. PPS polymers demonstrated similar in vitro and in vivo biocompatibility compared to poly(L-lactic-co-glycolic acid) (PLGA).