The purpose of this study was to evaluate the influence of elastic modulus of restorative materials and the number of interfaces of post and core systems on the stress distribution of three differently restored endodontically treated maxillary second premolars using 3D FE analysis. Model 1, 2 was restored with a stainless steel or glass fiber post and direct composite resin. A PFG or a sintered alumina crown was considered. Model 3 was restored by EndoCrown. An oblique 500 N was applied on the buccal (Load A) and palatal (Load B) cusp. The von Mises stresses in the coronal and root structure of each model were analyzed using ANSYS. The elastic modulus of the definitive restorations rather than the type of post and core system was the primary factor that influenced the stress distribution of endodontically treated maxillary premolars. The stress concentration at the coronal structure could be lowered through the use of definitive restoration of high elastic modulus. The stress concentration at the root structure could be lowered through the use of definitive restoration of low elastic modulus.