The morphology, miscibility, and specific interactions of paclitaxel (PTx) with a family of polyhedral oligosilsesquioxane (POSS)-based biodegradable thermoplastic polyurethanes (POSS TPUs) were investigated systematically using wide-angle X-ray diffraction (WAXD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). These POSS TPUs incorporate an alternating multiblock structure formed by POSS hard segments and the soft segments composed of polylactide/caprolactone copolymer (P(DLLA-co-CL)). They feature variable poly(ethylene glycol) (PEG) content from 0 to 14 wt % through adjusting the poly(ethylene glycol) (PEG) molecular weight in P(DLLA-co-CL) soft segments of fixed molar mass of Mn = 12 kg/mol and further to 52 wt % utilizing pure PEG Mn = 1 kg/mol in the soft segments. Using WAXD, it was found that PTx is amorphous in all proportions in the PTx/POSS TPU blends prepared using a solution-casting method. Interestingly, the PTx not only exhibits excellent misc...