Research suggests that self-affirmation can reduce threat in a multitude of domains (e.g., stereotype threat). Given the capacity for self-affirmation to reduce threats to the self of various types, the current work examined the capacity for self-affirmation to reduce outgroup prejudice. Outgroup prejudice toward groups that have traditionally been stigmatized in the U.S. (i.e., Muslims, Atheists, African Americans) were explored. Mediating mechanisms (self-compassion, intergroup anxiety) and moderating mechanisms (collective self-esteem) were also examined. In Studies 1 and 2, it was predicted that as compared to a control condition, participants that engaged in a self-affirmation condition would show less prejudice and more positive outgroup attitudes, on measures of outgroup attitudes and job candidate evaluation ratings. In Study 2, a candidate condition had participants review either an African or White American job candidate for a job, and the interactive effects with this candidate condition and self-affirmation were examined. Under some circumstances, self-affirmation led to higher ratings of outgroup attitudes and lower levels of prejudice. Specifically, significant and marginal main and interactive effects of self-affirmation and candidate condition were found. Including covariates led to relationships that emerged as marginal or significant for self-affirmation or its interaction with candidate conditions. Covariates (i.e., political ideology, religion, motivation to control prejudice) were also marginal or significant predictors of the majority of the outcomes. Finally, significant effects of counterbalancing influenced some of the outcomes and intergroup anxiety, and interacted with candidate on some of the outcomes. Taken together, the results of the current studies suggest that self-affirmation can indeed improve attitudes among religious and racial outgroup members in the United States. However, other demographic and individual difference variables influenced this effect. Examining conditions to reduce prejudice are important, because understanding ways of reducing prejudice will help foster harmony between members of different social groups.