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Can the hegemony of Western epistemologies anchor processes of inequality? In this paper we consider how epistemological hegemony in science, engineering and health (SE&H) fields perpetuate disadvantages for students who enter higher education with marginalized epistemologies. Drawing from indepth interviews with Native American students enrolled at two U.S. researchoriented universities who adhere to or revere indigenous epistemologies, we find that epistemological hegemony in Western SE&H degree programs disadvantages students through three processes. First, this hegemony delegitimizes Native epistemologies and marginalizes and silences students who value them. Second, in the process of learning Western epistemologies, SE&H courses occasionally require students to participate in pedagogical practices that directly challenge indigenous ways of knowing. Third, students encounter epistemological imperialism: The majority of students in the sample working to earn SE&H degrees do so in order to return to tribal communities to “give back,” yet, because U.S. laws regulating the practice of SE&H extend onto tribal lands, students must earn credentials in epistemologies that devalue, delegitimate, and threaten indigenous knowledge ways. We examine how students navigate these conflicts and end with a discussion of the implications of these findings for SE&H education and for understanding the ways epistemological hegemony can reproduce inequality.