This pilot study evaluated the feasibility of implementing an evidence-based, culturally adapted HIV intervention with substance-using African American men in a prison setting. We recruited 60, soon-to-be released African American male prisoners from a larger study (N = 211) to be randomly selected for participation in the group-based HIV intervention, Real Men Are Safe–Culturally Adapted (REMAS-CA). Participants who were not selected for participation in the intervention received standard Centers for Disease Control and Prevention HIV prevention counseling education, provided during participant assessment in the larger study. Nearly all of the participants who were selected to participate (87%) completed the REMAS-CA intervention. To examine feasibility, data were collected about any revisions made to the HIV intervention components for the prison setting, time needed to implement the program in full, details of implementing the intervention to ensure participation and maintain retention, and participant perception of the intervention. Revisions to the intervention included reducing the number of sessions from five to three, modifying the protocol language based on the setting, and removing six activities deemed inappropriate and/or unallowable by the prison officials. The cultural considerations and intervention, overall, were well received by the participants. However, several revisions made specific to the prison and its administration could affect the potential effectiveness of the intervention. Future research is needed to determine the effectiveness of REMAS-CA among this community.