Although the rate of HIV infection among US prison inmates is considerably higher than that of the general population, little is known about age-related changes in HIV-infected inmates over the last decade. This study of the nation’s largest state prison system examined (1) whether the mean age of the HIV-infected inmate increased over the last decade, and (2) whether the prevalence of HIV and associated comorbidities varied according to age. The study population included all 230,103 inmates incarcerated in the Texas prison system for any duration during 2014. A separate analysis was conducted on all HIV-infected inmates incarcerated between 2004 and 2014. Information on medical conditions and demographic factors was obtained from an institution-wide electronic medical record system. From 2004 to 2014, the mean age of HIV-infected inmates in the prison system increased from 39.3 to 42.5 years, compared to an increase of 36.1–37.9 for all Texas prison inmates. Multivariable logistic regression was used to assess the independent contributions of multiple demographic and clinical covariates in predicting the binary outcome, HIV infection. The model showed that, in 2014, HIV infection was elevated in inmates who were aged 40–49 years (OR = 3.1; 95% CI 2.7–3.3), aged 50–59 years (OR = 2.4; 95% CI 2.1–2.7), African American (OR = 3.0; 95% CI 2.8–3.3), and in those with several chronic diseases, including chronic obstructive pulmonary disease (OR = 1.7; 95% CI 1.5–1.9), hepatitis C (OR = 2.7; 95% CI 2.5–3.1), major depressive disorder (OR = 1.7; 95% CI 1.5–2.1), bipolar disorder (OR = 2.3; 95% CI 1.8–2.8), and schizophrenia (OR = 1.5; 95% CI 1.3–1.8). Among HIV-infected inmates (n = 2960), the percentage with comorbid disease increased in a linear fashion according to age (p < .01). Correctional health systems must adapt to address the evolving epidemiology of HIV among inmate populations.