Objectives: There has been a growing interest in glass ceramic systems with good esthetics, high fracture resistance and bonding durability, and simplified fabrication techniques using CAD/CAM. The aim of this study is to compare flexural strength before and after heat treatment of two lithium disilicate CAD/CAM blocks, IPS e.max CAD (Ivoclar Vivadent) and Rosetta SM (Hass), and to observe their crystalline structures. Materials and Methods: Biaxial flexural strength was tested according to ISO 6872 with 20 disc form specimens sliced from each block before and after heat treatment. Also, the crystalline structures were observed using field-emission scanning microscopy (FE-SEM, Hitachi) and x-ray diffraction (XRD, Rigaku) analysis. The mean values of the biaxial flexural strength were analyzed by the Mann-Whitney U test at a significance level of p = 0.05. Results: There were no statistically significant differences in flexural strength between IPS e.max CAD and Rosetta SM either before heat treatment or after heat treatment. For both ceramics, the initial flexural strength greatly increased after heat treatment, with significant differences (p < 0.05). The FE-SEM images presented similar patterns of crystalline structure in the two ceramics. In the XRD analysis, they also had similar patterns, presenting high peak positions corresponding to the standard lithium metasilicate and lithium disilicate at each stage of heat treatment. Conclusions: IPS e.max CAD and Rosetta SM showed no significant differences in flexural strength. They had a similar crystalline pattern and molecular composition.