Purpose: This study aimed to evaluate color changes in 3D-printed acrylic restorations of varying thicknesses and exposed to different post-curing durations. Materials and Methods: Three virtual full-contour maxillary central incisor crowns with different buccal thicknesses (1.0, 1.5, and 2.0 mm) were designed and manufactured using a 3D printer and a photopolymer (n = 9 per thickness group). The lightness, hue, and chroma of the restorations were measured at baseline (prior to post-curing) and again at 5 min intervals up to 30 min during the post-curing process using a spectrophotometer. Color changes (ΔE) were calculated by comparing the CIE L*, a*, b* coordinates at different time points to the baseline values. Repeated-measures analysis of variance and the Tukey’s post-hoc test were used for statistical analysis (α = .05). Results: The ΔE increased significantly within the first 5 min of post-curing and was more gradual thereafter in all thickness groups. The ΔE values were significantly higher in the 1.5 and 2.0 mm thickness groups compared to the 1.0 mm thickness group. The C* coordinate was seen to increase significantly within the first 5 min of post-curing, and did not change significantly afterward. Conclusions: During post-curing, the hue of a 3D printed polymeric restoration changed to yellowish and reddish shades, the brightness decreased, and the saturation increased. Most color changes occurred within the first 5 min of post-curing and were also more noticeable in thicker restorations.