Responses to highly active antiretroviral therapy (HAART) in correctional settings and their sustained benefit in prisoners after release are currently not known. To examine the human immunodeficiency virus type 1 (HIV-1) RNA level (VL) and CD4 lymphocyte response to HAART during incarceration and upon reentry to the correctional system, we conducted a retrospective cohort study of longitudinally linked demographic, pharmacy, and laboratory data from the Connecticut prison system. During incarceration, the mean CD4 lymphocyte count increased by 74 lymphocytes/μL, and the mean VL decreased by 0.93 log10 copies/mL (P < .0001). Fifty-nine percent of the subjects achieved a VL of <400 copies/mL at the end of each incarceration period. For the 27% of subjects who were reincarcerated, the mean CD4 lymphocyte count decreased by 80 lymphocytes/μL, and the mean VL increased by 1.14 log10 (P < .0001). Although HAART use resulted in impressive VL and CD4 lymphocyte outcomes during the period of incarceration, recidivism to prison was high and was associated with a poor outcome. More effective community-release programs are needed for incarcerated patients with HIV disease.