Objective: To determine if spiritual factors defined as positive spiritual coping, negative spiritual coping and spiritual resilience, are related to more positive health related outcomes (HROs), such as physical health, health related quality of life, well-being and CD4 counts and investigate if spiritual factors change the relationship between current substance use and parental substance abuse.Background: In 2022 African American Women were the second highest group to be diagnosed with HIV/AIDS disease, largely driven by personal and parental history of substance use disorder in African American Women which contributes to an increase in condomless sex with men with HIV. This leads women who have acquired HIV to rely on spiritual factors to deal with the reality of managing HIV/AIDS and the use of substances. Method: This study used a quantitative, cross-sectional internet survey design to understand the impact of spiritual factors related to specific health-related outcomes (HROs) in African American women with HIV. Regression analyses were conducted to examine the relationship between positive and negative spiritual coping, spiritual resilience and HROs. A moderation analysis was used to examine the ability of spiritual variables to moderate the relationship between current substance use and parental substance use. Based on prior knowledge the assumption is there is an association between parental substance abuse and current substance abuse which could then be moderated by spiritual factors. This relationship was examined and analyzed. Results: Thirty-eight Older African American Women (OAAW) from across the U.S. completed the internet survey. Significant results found that negative spiritual coping had a stronger impact in the research study than positive spiritual coping. In the unadjusted model, HRQOL and well-being both had inverse significant relationships with negative spiritual coping. When controlling for age and substance use, only HRQOL was statistically significant and inversely related. Positive spiritual coping was inversely related to HRQOL before controlling for age and substance use). After controlling for substance use and age, HRQOL was no longer significant. In the moderation analysis, positive spiritual coping moderated the relationship between current substance use and parental substance abuse. As positive spiritual coping increased, the relationship between current substance use and parental substance abuse strengthened. Conclusion: In this study, negative spiritual coping had a stronger effect on HRQOL outcomes and well-being than positive spiritual coping or spiritual resilience, suggesting that the use of negative spiritual coping impaired HRQOL in the participants. In addition, the finding that positive spiritual coping strengthened the relationship between personal and parental substance use was unexpected, as it is widely cited in literature that positive spiritual coping as a protective factor helps prevent drug use within families of people who engage in drug use. A possible explanation is that families who use drugs and have a strong family connection influence the individual’s risk of future substance use even when positive spiritual coping is practiced. Another explanation for the results is OAAW with difficult family influences rely heavily on positive spiritual coping. The associations of positive spiritual coping with the relationship between parental and individual substance use have not yet been fully elucidated but may be clarified through a future prospective study to look at positive spiritual coping over time