Polyurethanes are materials with a strong structure-property relationship. The goal of this research was to study the effect of a polyol blend composition of polyurethanes on its properties using a mixture design and setting mathematic models for each property. Water absorption, hydrolytic degradation, contact angle, tensile strength hardness and modulus were studied. Additionally, thermal stability was studied by thermogravimetric analysis. Area under the curve was used to evaluate the effect of polyol blend composition on thermal stability and kinetics of water absorption and hydrolytic degradation. Least squares were used to calculate the regression coefficients. Models for the properties were significant, and lack of fit was not (p < 0.05). Fit statistics suggest both good fitting and prediction. Water absorption, hydrolytic degradation and contact angle were mediated by the hydrophilic nature of the polyols. Tensile strength, modulus and hardness could be regulated by the PE content and the characteristics of polyols. Regression of DTG curves from thermal analysis showed improvement of thermal stability with the increase of PCL and PE. An ANOVA test of the model terms demonstrated that three component influences on bulk properties like water absorption, hydrolytic degradation, hardness, tensile strength and modulus. The PEG*PCL interaction influences on the contact angle, which is a surface property. Mixture design application allowed for an understanding of the structure-property relationship through mathematic models.