Objectives: The objectives of this in vitro study were: 1) to test the agreement among color coordinate differences and total color difference (ΔL*, ΔC*, Δh°, and ΔE) measurements obtained by digital image analysis (DIA) and spectrophotometer, and 2) to test the reliability of each method for obtaining color differences. Materials and methods: A digital camera was used to record standardized images of each of the 15 shade tabs from the IPS e.max shade guide placed edge-to-edge in a phantom head with a reference shade tab. The images were analyzed using image-editing software (Adobe Photoshop) to obtain the color differences between the middle area of each test shade tab and the corresponding area of the reference tab. The color differences for the same shade tab areas were also measured using a spectrophotometer. To assess the reliability, measurements for the 15 shade tabs were repeated twice using the two methods. The Intraclass Correlation Coefficient (ICC) and the Dahlberg index were used to calculate agreement and reliability. Results: The total agreement of the two methods for measuring ΔL*, ΔC*, Δh°, and ΔE, according to the ICC, exceeded 0.82. The Dahlberg indices for ΔL* and ΔE were 2.18 and 2.98, respectively. For the reliability calculation, the ICCs for the DIA and the spectrophotometer ΔE were 0.91 and 0.94, respectively. Conclusions: High agreement was obtained between the DIA and spectrophotometer results for the ΔL*, ΔC*, Δh°, and ΔE measurements. Further, the reliability of the measurements for the spectrophotometer was slightly higher than the reliability of all measurements in the DIA.