Advances in HIV treatments have led to a greater focus on health-related quality of life (HRQOL) among people living with HIV/AIDS. The current study examined HRQOL among women living with HIV/AIDS, with a special emphasis on the roles of personal and household membersâ alcohol and drug use. Women in HIV care (N=378) completed a comprehensive assessment. HRQOL was measured using a modified version of the 12-Item Short Form Health Survey (SF-12); scores were derived for the mental and physical composite summaries (MCS and PCS, respectively; lower scores reflect poorer HRQOL). The Alcohol Use Disorders Identification Test (AUDIT), the Risk Assessment Battery and the 90-day Timeline Followback (TLFB) were used to measure recent alcohol and drug use. Household membersâ substance use were assessed by asking participants about the alcohol/drug status of persons with whom they live. Multivariate generalized linear models were used to estimate the linear association between MCS and PCS scores and demographic characteristics, and personal and household membersâ alcohol and drug use. We found lower MCS scores were significantly associated with personal alcohol use, lower income, not being African American, and living with someone with alcohol or/and drug problems. Lower PCS scores were significantly associated with older age and being divorced, separated or widowed. Compared to never married, being married was associated with higher PCS scores. Findings indicate that personal alcohol use and household membersâ substance use are independently associated with lower mental HRQOL. Universal screening and targeted interventions for alcohol use by the patient or household members may offer potential strategies for improving mental health quality of life among women living with HIV/AIDS.