Published assessments of religion and health scholarship observe the substantial need for the study of African American spirituality, and that what is available has implicated this cultural production as helpful and supportive of good health yet inhibitive in end-of-life decision making. This qualitative study from semi-structured interviews with African American prostate cancer patients finds spirituality as helpful to sustaining patients in their decisions to risk medical research although patients determine their decision to accept risk based on their understanding of the medical science presented to them. They are comforted by the agency available to them through bioethical principles and practices, most notably, informed consent. The findings of this study contest the centrality of the Tuskegee narrative popularly believed to be inhibitive to African American clinical trial participation as well as the over-simplification of the relationship between religion and African Americans’ cancer fatalism widely held among members of the health professions. The study acknowledges that structural issues prevent too many African Americans from access to the option of clinical trial participation. Two constructs are offered: a cultural sociological approach (Jeffrey Alexander; Gordon Lynch) to re-imagining Tuskegee as a sacred rhetoric, and a sociological approach to risk acceptance and risk taking referencing institutionalized religion; both constructs are derived from Durkheimian theory. These solutions are offered as responses to the data that emerged through the qualitative research and existing treatments of religion and health in African American religious scholarship. This study suggests that there is a shifting paradigm in which more African Americans will merge their spirituality with scientific knowledge to increase medical research participation with the long term aim of reducing health disparities. In turn, additional theoretical frameworks will emerge beyond the closed loop epistemology inherent in Durkheim’s theory. The research agenda begun here points to implications for theory and practice in fields including African American Religions, pastoral theology, health policy, health services, and bioethics.