Statement of problem: The microstructure and processing methods used to produce any dental restoration might affect the final mechanical outcomes as well as the clinical success. Objectives: The purpose of this study was to evaluate the fracture resistance of lithium disilicate and zirconia reinforced lithium disilicate ceramic crowns constructed using two processing techniques after fatigue loading namely, CAD/CAM technique and pressing technique. The marginal integrity of the crowns was examined before and after fatigue loading. Methods: A total number of thirty-two freshly extracted maxillary first molars were collected. The teeth were chosen to be of similar bucco-lingual and mesiodistal dimensions. The teeth were mounted vertically into epoxy resin templates. Full coverage all-ceramic preparation was performed for all samples using a standardized technique. The prepared teeth were randomly divided into four equal groups (n=8) according to the all-ceramic materials and technique used for crown fabrication as follows: Group I: IPS e-max CAD(EC): eight prepared teeth were restored with machinable lithium disilicate glass ceramics. Group II: Celtra Duo(CD): eight prepared teeth were restored with machinable zirconia-reinforced lithium disilicate glass ceramics. Group III: IPS e-max Press (EP): eight prepared teeth were restored with pressable lithium disilicate glass ceramics. Group IV: Celtra Press (CP): eight prepared teeth were restored with pressable zirconia-reinforced lithium disilicate glass ceramics. The crowns were cemented using self-adhesive resin cement (Rely X Unicem). Vertical margin gap distance of all the crowns was measured using a stereomicroscope. Following vertical marginal gap distance measurements, the samples were subjected to fatigue cyclic loading for 60000 cycles which is equivalent to six months clinical service. The vertical marginal gap distance for all samples were subsequently remeasured after the fatigue loading testing. Fracture resistance test was done using universal testing machine. The fracture load was recorded in Newton. Data was collected, tabulated and statistically analyzed.