Rationale. Studies linking discrimination to poor mental and physical health constitute one of the most robust branches of health inequities research. For more than two decades, and in more than a dozen countries, scholars working in this field have used the Everyday Discrimination Scale (EDS) to assess perceptions of discrimination. Two recent studies (Harnois et al., 2020; Harnois et al., 2019) cast doubt on the instrument's psychometric equivalence across diverse social groups, however. Objective. Our study builds on these previous analyses using a larger and more ethnically and geographically diverse sample of adults in the US, the Collaborative Psychiatric Epidemiology Surveys. Method. Multi-group Confirmatory Factor Analyses were carried out to compare the configural, metric, and scalar structures of the EDS. Results. Analyzing perceptions of racial/ethnic discrimination, we find a lack of equivalence across race/ethnicity, consistent with previous research. Reports of general mistreatment are found to be equivalent across gender-based groups, but not across race/ethnicity, age- or education-based groups. Conclusions. Our study provides further evidence that the EDS should be used with caution, particularly when assessing general perceptions of discrimination, and particularly when making cross-group comparisons. Measurement invariance is required to effectively assess the relationship between discrimination and health; further refinement of the scale may be needed to achieve this goal.