The aim of the study was to evaluate the marginal adaptation of various hybrid ceramics inlays before and after thermal cycling. Twenty-four extracted human molars were received inlay preparation, and randomly divided into three groups (n = 8/group). Specimens were restored with Ceramage by experienced technician, Enamic or Lava Ultimate by CAD/CAM using CEREC Omnicam. After cementation, all restorations were subjected to thermal cycling. Marginal gaps were measured under a stereomicroscope. The overall mean marginal gaps of the three groups were significantly different (p < 0.05) before thermal cycling, which were all within the clinically acceptable range. The digital intraoral impression and CAD/CAM systems did not show superior accuracy compared to the traditional technique, during the hybrid ceramic inlays manufactured operation. Thermal cycling had no effect on marginal adaptation of the different hybrid ceramic inlays (p > 0.05). Gingival margin presented larger gaps compared to occlusal and axial margin in all hybrid ceramic inlays.