Statement of problem: Dental shade guides are used to evaluate tooth color prior to restorative and prosthodontic procedures and are subjected to disinfection after use. The effect of disinfection on shade guides has not been thoroughly investigated. Purpose: The purpose of this project was to study the effect of disinfectants on changes in color of shade tabs. Materials and Methods: Changes in color (Delta E) of Vita Classic Shade Guide tabs were measured with a Vita Easyshade spectrophotometer and calculated after being subjected to Cavicide, Asepticare TB, Sporicidin, and distilled water (control) over a simulated two-years period. Statistical analysis was accomplished by a two-way analysis of variance followed by Tukey's HSD test (p<0.05) Results: There was a significant difference in the degree of shade tab color change depending on the type of disinfectant used (F=153.2, p=0.0005). There was no significant difference in the amount of shade tab color change that occurred after disinfection between the different shade tabs used (F=0.611, p=0.87) nor a significant interaction between the type of disinfectant and the different shade tabs used (F=0.7, p=0.92). Aspecticare TB showed the least significant amount of change (Delta E=0.401), Sporicidin (Delta E=0.889) and the control (Delta E=0.969) showed significantly more color change than Asepticare TB but less color change than Cavicide (Delta E=1.198). Conclusion: It has been reported that human observers can be expected to detect color differences of 1 Delta E unit under standardized laboratory conditions (Kuehni 1979). In the oral cavity, however, an average change of 3.7 Delta E units could still allow teeth to be matched as having the same color (Johnson 1989). Therefore, while the results are significant, they may not be clinically important.