The key cause of HIV transmission is failure to provide adequate information about HIV/AIDS which is a substantial public health issue in low and middle-income countries. While global health coverage continues, there is still little understanding of HIV/AIDS among women of reproductive age (15–49 years) in Ethiopia. Therefore, the purpose of this study was to identify the determinants of comprehensive knowledge of HIV/AIDS among women of reproductive age in Ethiopia.

A secondary data analysis was employed using the 2016 Ethiopian demographic and health survey data. Data were extracted about comprehensive knowledge of HIV/AIDS among women of reproductive age. We used multi-variable mixed-effect binary logistic regression to identify factors associated with comprehensive knowledge of HIV/AIDS among women of reproductive age. The adjusted odds ratio with 95% confidence interval was used to declare statistical significance.

We found that having primary (AOR = 1.75, 95% CI 1.56–1.97),secondary (AOR = 2.74, 95% CI 2.33–3.22), and higher (AOR = 4.07, 95% CI 3.32–4.99) educational statuses, being in highest wealth quintiles; richer (AOR = 1.20, 95% CI 1.01–1.43) and richest (AOR = 1.51, 95% CI 1.22–1.87), knowing the place for HIV test (AOR = 2.13, 95% CI 1.88–2.42), use of traditional contraceptive method (AOR = 1.93,95% CI 1.12–3.35), female household head (AOR = 1.18, 95% CI 1.07–1.31), watching television (AOR = 1.22, 95% CI 1.06–1.41) and own mobile phone (AOR = 1.18, 95% CI 1.05–1.33) were positively associated with comprehensive knowledge of HIV/AIDS among women of reproductive age in Ethiopia.

Women with higher education and higher wealth quintiles, knowing the place of HIV test, watching television, a traditional contraceptive method use, having a mobile phone and being in female headed household were positively associated with comprehensive knowledge of HIV/AIDS among women of reproductive age in Ethiopia. Programs working on HIV/AIDS should target women based on the identified factors so as to scale up their comprehensive knowledge towards HIV/AIDS. In this context, the media should actively contribute to raising awareness of HIV/AIDS.