Background: We explored ethical challenges in conducting psychiatric or mental health research with incarcerated people. Methods: Semistructured interviews were conducted with 87 people who were researchers; institutional review board (IRB) chairs, members, and prisoner representatives; research ethicists; and prison administrators with experience in and knowledge about the conduct of research in correctional settings. NVivo 9.0 was used to conduct grounded theory analysis of responses to the question: “What would you say are the top three ethical challenges to conducting psychiatric or mental health research with incarcerated people?” Results: Key informants identified autonomy and consent, balancing the potential for direct benefit with the risk for harm, and access to and standards of psychiatric care in correctional facilities as the three most important ethical challenges. The characteristics of incarcerated individuals, the nature of correctional systems, and federal regulations for oversight of prisoner research provided the contextual framework for these challenges. Conclusions: Findings from this study provide insights into ethical challenges affecting the conduct of psychiatric and mental health research with incarcerated individuals. Given the potential benefit to incarcerated people from access to participation in research, these ethical challenges should be addressed.