The study of the effect of the diisocyanate structure on the microstructure and macroscopic properties of polyurethanes was the main aim of this work. Biodegradable segmented thermoplastic elastomeric polyurethanes based on a poly(hexamethylene carbonate-co-caprolactone)diol (PHM-co-PCL) as soft segment were synthesized using 1,4-butanediol (BD) as chain extender and both 4,4'-diphenylmethane diisocyanate (MDI) and 1,6-hexamethylene diisocyanate (HDI) as components of the hard segment by the two shoot synthesis procedure. Microphase structure and properties were analyzed using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) as complementary techniques, used to characterize thermal transitions of the polyurethanes and to assign them to determinate functional groups interactions. Gaussian deconvolution technique was used to decompose carbonyl region in four peaks and to study the hydrogen bonding within the different polyurethanes. Both DSC and FTIR showed that MDI-based biodegradable polyurethanes were less phase segregated than to those based on HDI, and thus that diisocyanate structure has an important role on microdomain composition and polyurethanes properties. Macroscopic properties as hardness and water-polymer contact angles are related to polyurethanes microphase compositions.