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

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... s 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.