PURPOSE: People with the Human Immunodeficiency Virus (HIV) frequently report a high incidence of medical problems, low quality of life (QOL), and sedentary lifestyles. We examined the effect of increased weekly walking on medical outcomes and QOL in HIV positive substance users. METHODS: Researchers collected data on 24 HIV positive DSM-IV substance users (n=13 men; n=11 women) at baseline and 2 months. The Functional Assessment of the Human Immunodeficiency Virus (FAHI) was administered to assess QOL as related to global function, acceptance of illness, capacity to work, coping skills and self esteem; the medical composite score of the Addiction Severity Index (ASI) to assess the severity of medical problems commonly impacted by substance use; and the Paffenbarger Physical Activity Questionnaire (PPAQ) to determine weekly walking distance. Regression analysis in Stata v. 11.1 determined if changes in weekly walking distance predicted QOL and medical outcomes from baseline to 2 month follow-up. RESULTS: As subjects increased daily walking from baseline (1.08 ± 0.79 miles) to 2 months (1.30 ± 1.05 miles), ASI medical composite scores decreased (B =-0.50, p =.03). Changes in weekly walking also trended (B =.42, p=.08) toward higher global functioning with an increase in FAHI functional scores. CONCLUSIONS: Participants who increased their walking distance reported a reduction in the severity of medical problems and a trend toward improved QOL. Additional monitoring over another 2 month period will determine if these favorable relationships persist. Supported by: NIH R01DA022739, P30-DA023918 and, M01-RR06192.