African American women have among the highest HIV/AIDS and hepatitis B and C incidence rates in the United States, especially among those homeless or incarcerated. The objective of this study was to evaluate the Health Enlightenment, Awareness and Living Intervention, designed to decrease HIV/AIDS, hepatitis and related risky behaviors. The thirteen-session intervention was implemented among homeless and formerly incarcerated low-income African American women, ages 18 to 55, in Atlanta, Georgia from 2006 to 2010. A single group repeated measures study design was employed and consisted of a pre-test (n = 355) group, an immediate post-test (n = 228) group with a response rate of 64%, and a six-month follow up (n = 110) group with response rate of 48%, completing a 135-item survey. Paired-sample t-tests, McNemar tests, and repeated measures ANOVA were applied to compare survey results. Participants demonstrated statistically significant increases in hepatitis B and C knowledge over time (p < 0.001). Statistically significant decreases were also reported for unprotected sex in exchange for money, drugs or shelter (p = 0.008), and sex under the influence of drugs or alcohol (p < 0.001). Reported substance use decreased with statistical significance for alcohol (p = 0.011), marijuana (p = 0.011), illegal drugs (p = 0.002), and crack/cocaine (p = 0.003). Findings broaden the evidence base related to the effectiveness of HIV/AIDS and hepatitis risk reduction interventions designed for homeless and previously incarcerated African American women.