For the first time, we report the optimization of reaction conditions for the synthesis of novel thermally modified optically active pol (amide-imide-ether-urethane)s (PAIEU)s prepared by diisocyanate route. The effects and importance of different reaction parameters such as reaction temperature, reaction time, and soft segment length on the controlling of chain growth of the resulting copolymers were investigated. Thus, four different series of PAIEUs based on different molecular weight of polyethylene glycol (PEG)s were synthesized through the reaction of a new imide containing diacid, with 4,4'-methylene-bis-(4-phenylisocyanate) (MDI). A linear correlation was constructed using experimental values of viscosities of the resulting copolymers based different molecular weights of PEGs at different reaction temperatures, and reaction time. The influence of each parameter was studied by factorial design analysis. Analysis of variance (ANOVA) was also used to evaluate the significance of the linear regression model (correlation). The statistical parameters reveal strong evidence that the constructed correlation is reliable.