The polycondensation of isophorone diisocyanate (IPDI) with dodecanediol has been performed in aqueous miniemulsion in order to obtain hydrophobic polyurethane dispersions. The influence of several factors, such as temperature, surfactant, and catalyst, on the molecular weight has been studied in detail. It has been found that the use of hydrophobic organo-tin catalysts, a solvent of the polyaddition medium, or an off-stoichiometric ratio of the isocyanate and the diol component permits to considerably increase the molecular weight of the polymer. It is also shown that hybrid polymer nanoparticles based on polystyrene/polyurethane (PS/PU) or poly(butyl acrylate)/polyurethane (PBA/PU) can been synthesized using a one-pot procedure.