To evaluate the long-term color stainability, translucency, and contrast ratio (CR) of different resins used to fabricate interim prostheses after immersion in acidic/staining solutions. A total of 160 specimens were divided into 16 groups (n = 10) according to the material (heat-polymerized acrylic resin [HPAR], auto-polymerized acrylic resin [APR], nanoparticulated bis-acrylic resin [BR], and prefabricated poly(methyl methacrylate) block for CAD/CAM [CADR]) and immersion solutions (artificial saliva, cola beverage, coffee, and red wine). A spectrophotometer was used before and after each immersion period (7, 14, 28, 90, and 180 days). Color differences (CIEDE2000 and CIELab) were calculated. A three-way repeated-measures analysis of variance and Bonferroni test (α = .05) were used. After 180 days, the APR presented the highest value for coffee and the CADR presented the smallest value for the cola (P < .001). For the CR, the highest values were obtained at 180 days for BR in coffee (1.35) and wine (1.18) (P < .001). Higher translucency parameters were obtained in the BR and CADR in the initial, 14, 28, and 90 days (P < .001). From the greatest to the smallest staining potential, the solutions were classified as: wine > coffee > cola beverage > saliva, while for the materials as: APR > BR > HPAR > CADR. The knowledge of the long-term optical behavior of interim prosthetic materials is important for clinicians to decide which material to use to match the dietary intake of their patients and their esthetic demands. Prefabricated blocks for CAD/CAM systems have been shown to maintaining their optical characteristics even after a long period of immersion in acidic/staining solutions.