Objective: The purpose of this study was to examine the fracture strength and surface microhardness of computer-aided design/computer-aided manufacturing (CAD/CAM) materials in vitro. Materials and Methods: Mesial-occlusal-distal inlays were made from five different CAD/CAM materials (feldspathic ceramic, CEREC blocs; leucite-reinforced ceramic, IPS Empress CAD; resin nano ceramic, 3M ESPE Lava Ultimate; hybrid ceramic, VITA Enamic; and lithium disilicate ceramic, IPS e. max CAD) using CEREC 4 CAD/CAM system. Samples were adhesively cemented to metal analogs with a resin cement (3M ESPE, U200). The fracture tests were carried out with a universal testing machine. Furthermore, five samples were prepared from each CAD/CAM material for micro-Vickers hardness test. Data were analyzed with statistics software SPSS 20 (IBM Corp., New York, USA). Results: Fracture strength of lithium disilicate inlays (3949 N) was found to be higher than other ceramic inlays (P < 0.05). There was no difference between other inlays statistically (P > 0.05). The highest micro-Vickers hardness was measured in lithium disilicate samples, and the lowest was in resin nano ceramic samples. Conclusion: Fracture strength results demonstrate that inlays can withstand the forces in the mouth. Statistical results showed that fracture strength and micro-Vickers hardness of feldspathic ceramic, leucite-reinforced ceramic, and lithium disilicate ceramic materials had a positive correlation.