A series of segmented polyurethanes obtained from perfluoropolyether (PFPE) and isophorone diisocyanate (IPDI) were studied by using quantitative thermal analysis. The glass transition behavior of the segregated phases of the segmented copolymers, compared to the corresponding amorphous homopolymers, was characterized in order to determine the dependence of the phase separation on the composition. The glass transition was observed to shift and broaden for both the hydrogenated and the fluorinated phase, reducing the corresponding content in the polymer, and the measured Deltac(p) on the segregated phases deviates from the expected ones according to the homopolymer values. To investigate the effects of the size of the separated domains and of the interfacial constraints on the glass transition behavior, heat capacity measurements were carried out on PFPE models with perfluorinated or methilolic chain ends absorbed on amorphous silica. The chain mobility reduction associated with a nanoscopic confinement is responsible for the effects on the glass transition measured by DSC. This phenomenon seems to rule the observed similar behavior within the polyurethane series investigated in the present work.