The effect of staining beverages on the color of dentures made with computer-aided design and computer-aided manufacturing (CAD-CAM) is unknown. The purpose of this in vitro study was to evaluate the stainability of acrylic resins used in CAD-CAM–fabricated complete dentures compared with conventional materials. Acrylic resin denture teeth from 3 different manufacturers (2 conventional and 1 milled) were obtained (N=45). Denture base acrylic resin specimens were made with 3 different techniques (compression molding, injection molding, and milling) (N=45). Conventional and/or milled acrylic resins were used to make specimens comprising both denture teeth and denture base acrylic resins (4 conventional, 2 milled denture bases with bonded teeth, and 1 all-milled) (N=105). All specimens were then immersed in coffee, red wine, or distilled water as control. The CIELab color differences between before and after immersion were determined by using a VITA Easyshade spectrophotometer. The tooth-denture base interface of the denture blocks was evaluated visually for the presence of stain. The CIELab data were analyzed by using ANOVA, and chi-square test was used for visual assessment (α=.05). Significant interactions were found between each acrylic resin material and each staining solution immersion when compared with distilled water immersion (P <.001). Denture teeth had similar color change after immersion in coffee (P =.149), while the most pronounced color change was observed with Portrait teeth upon immersion in wine (P <.001). Injection-molded denture base specimens exhibited less color change upon staining in wine than compression-molded or milled specimens (P <.001). Upon staining in coffee, milled specimens were not significantly different from injection- (P =.053) and compression-molded specimens (P =.180). The chi-square test showed a significant association between processing technique and stain accumulation at the tooth-denture base interface when evaluated visually (P <.001). Stain accumulation was greatest with compression-molded specimens (58%), followed by injection-molded (43%) and milled specimens with bonded teeth (8%). Monolithic teeth with milled denture base had no stain deposits at the tooth-denture base interface. The stainability of milled acrylic resins was no better than that of conventional materials. However, CAD-CAM milled denture blocks with teeth and base acrylic resins had greater resistance to stain accumulation at the tooth-denture base interface than those of conventional processing methods. [ABSTRACT FROM AUTHOR]