As a consequence of their mechanical properties, thermoplastic poly(ester-urethane)s (TPEUs) have been extensively examined for their potential applications in biomedical engineering. The incorporation of bio-derived small molecules, such as amino acid derivatives, as chain extenders may allow for more biodegradable hard segments, which result in nontoxic degradants. TPEUs were synthesized using modified 2-aminopropane-1,3-diol (serinol) extenders, ethyl (1,3-dihydroxypropan-2-yl)carbamate (C-3c), and 1-(1,3-dihydroxypropan-2-yl)-3-ethylurea (C-3u) in order to determine the effect of extender side group functionality on the properties of the resultant materials. The TPEUs were synthesized with varying percentage "hard" segment (%HS) using poly(e-caprolactone) (PCL) and 1-isocyanato-4-[(4-isocyanatocyclohexyl)methyl]cyclohexane (H12MDI) as the polyol and diisocyanate, respectively. It was found that by controlling the %HS and side group functionality, the thermal and mechanical properties of the materials could be tuned. Furthermore, the selection of extender was