Taiwan is experiencing an outbreak of human immunodeficiency virus infection among injection drug users. The purpose of the study was to determine the impact of a Transtheoretical Model-based HIV education program among drug-dependent inmates. A single group pre/post design was used to evaluate shortened impacts among 136 inmates who were arrested for illicit drug use and had attended a brief HIV education program in 2005. A repeated-measures analysis of variance indicated positive changes in AIDS knowledge (F > = 104.16, p < 0.001), self-efficacy to reduce HIV-risk behaviors (F = 26.5, p < 0.001), and readiness of change on substance use (F = 4.83, p = 0.03). The study findings showed that a brief TTM-based HIV education program can be effective for drug-dependent inmates.