Endodontically treated teeth often require 360° ferrule to retain post and core restoration. The literature support on scientific evidence of partial ferrule is limited, hence this study was conducted to evaluate the fracture resistance of two post and core systems, i.e., Edelweiss and glass fiber post and core system with varying ferrule locations. About 54 extracted mandibular 1st premolars were divided into Edelweiss post and core (Group A) and glass fiber post and core (Group B). They were further subdivided into 3 groups each (Partial functional, partial non-functional, and circumferential). A standardized endodontic procedure was carried out on all the specimens. For group A, an Edelweiss drill of 1.4 mm was used to prepare the post space. Canals were then etched, a bonding agent was applied and posts were luted with paracore resin. For group B, post space was prepared with a straight fissure bur, followed by the same procedure as that of group A. Core build-up was done with composite resin. Cast crowns were fabricated and cemented with GIC. Fracture resistance was evaluated with UTM with a compressive load capacity of 1000 N until fracture occurred. The results of this study stated that in the Edelweiss group partial functional ferrule showed higher fracture resistance and in the glass fiber group circumferential ferrule showed higher fracture resistance. The study also showed that MOF is favorable in all the groups. The type of ferrule was one of the factors that affected the fracture resistance of Edelweiss and Glass fiber post and core group of specimens. The study also concluded that there was a predominant favorable mode of fracture across all groups, in all different ferrule locations. This study opens multiple avenues and methods in tooth restoration and shows that even a partial functional ferrule is sufficient for restoration, provided the right system is used. How to cite this article: Jadhav PD, Shetty R, Mehta D, et al. Comparative Evaluation of Fracture Resistance in Different Post and Core Systems with Varying Ferrule Locations: An In Vitro Study. J Contemp Dent Pract 2024;25(5):480-485.