OBJECTIVES: The purpose of this study was to evaluate the effect of high-translucent zirconia thickness and substrate shade on the final color of the restoration. MATERIAL AND METHODS: A total of 60 high-translucent monolithic zirconia disks were prepared using a CAD/CAM system. They were placed on composite substrates with A2, A3.5, and C3 colors (n = 10). The color differences (ΔE) of the ceramic disks on the A3.5 and C3 substrate compared to the control group (A2) were calculated and compared with acceptable thresholds (ΔE = 5.5) and perceptible thresholds (ΔE = 2/6). A one-sample t-test and repeated measures ANOVA were used to analyze the data statistically. RESULTS: The highest ΔE values were observed when comparing two zirconia disk thicknesses on the A3.2 substrate without cement (ΔE = 5/65). The lowest value of ΔE compared to the control group (A2) was related to the disk with 1 mm thickness on the A3.5 substrate (ΔE = 2/54), and the highest value was for the disk with 0.6 mm thickness on the C3 substrate (ΔE = 4/88). CONCLUSIONS: Using the zirconia disk with a 1 mm thickness on the C3 structure and a disk with a 0.6 mm thickness on the A3.5 structure with the presence of F2 cement can achieve an acceptable color difference (value of 5.5).