It is very important for clinicians to provide restorative treatments that provide durability for endodontically treated teeth. Trauma, occlusal premature contact, and features of teeth are some of the issues that can cause vertical root fractures (VRFs) in root canal-treated teeth. The aim of this 3-D study was to compare stress distribution on mandibular premolar teeth when using a variety of post designs instrumented with different rotary systems. Six mandibular premolar teeth were instrumented with the following tools: ProTaper Next, WaveOne (WO), Reciproc (R), ReciprocBlue (RB), F6-Skytaper, and TF-Adaptive. Teeth were scanned using cone beam computed tomography (CBCT) and the images were transferred to the Catia V5R25 software. Data were recorded in a stereolithography (STL) format. Four different post systems were used, fabricated from metal, fiber, zirconia, and titanium, respectively. Dentin, gutta, post, core, and crown models were added to the solid model. ANSYS V17.2 finite element analysis (FEA) software was used to determine stress distribution on each assembly. Finite analysis models were created that allowed for the calculation of stress distribution of 250-N loading at a 45° angle and vertical in relation to the roots. The maximum principal stress and von Mises values were higher under oblique loading on the roots. The F6-Skytaper and WO systems showed lower stress than other systems. The TF-Adaptive instrument showed higher stress distribution than the other models. Fiber and titanium posts showed lower stress than others. The F6-Skytaper, R, and RB instruments were found to be most effective in terms of displacement of the crown, resulting in the lowest stress values. Fiber and titanium posts showed better results than other post systems, while root canals instrumented with the F6-Skytaper and WO instruments were less likely to result in root fractures.