We investigated four polyurethanes that were synthesized with different hard segments and four commercial polyurethanes for in vivo biostability. The four polyurethanes with the varying hard segments were based on a 3:2:1 mole ratio of methylene diphenylene diisocyanate (MDI) or methylene dicyclohexane diisocyanate (H12MDI), butanediol (BD) or ethylene diamine (ED) and polytetramethylene oxide (PTMO) (MW = 1000). Four commercial polyurethanes were also used: Biomer, Pellethane, Medtronic experimental C-19 (C-19) and Medtronic experimental C-36 (C-36). Films of the polymers were implanted subcutaneously in rats for up to 12 wk to assess their biostability. Polymer films were implanted either with a 100% strain applied or in the unstrained state. Measurement of tensile properties, molecular weight and surface properties before and after implantation assessed the stability of each of the polymers. Surface cracking was observed with scanning electron microscopy and the extent and depth of cracking were determined. Pellethane, C-19 and C-36 showed the least evidence of degradation, although all underwent strain-induced phenomena that decreased their tensile elongation when an external force was applied. After implantation, the BD chain-extended polymers retained their tensile properties better than ED chain-extended polymers. H12MDI-based polyurethanes were more susceptible to surface cracking and molecular weight changes than MDI-based polyurethanes, possibly due to the lack of a crystallizable hard segment.