Background: Globally, HIV is the leading cause of death among women of the reproductive age and unprotected sex is the main driver of HIV transmission. Lack of accurate and complete knowledge is one of the major causes of increase in the number of new HIV infections among women in Africa. This study was aimed at finding out factors associated with comprehensive knowledge among women in the reproductive age group of 15-49 years in Uganda. Methods: Data used was drawn from 2011 Uganda Demographic Health Survey (UDHS). Logistic regression model was used for analysis. Results: Only (38%) of the respondents had comprehensive knowledge of HIV. Women in lower wealth quintile had less comprehensive knowledge compared to those in the highest quintile (OR=1.28). The study also found out that the older women aged 45-49 were more knowledgeable to HIV (OR=1.46) than young ones. Women who had access to radio were associated with increased odds (OR=1.11) of high knowledge on HIV than those without. High knowledge to HIV was also associated with women who had ever tested for HIV (OR=1.20) and also increased with level of education (OR=1.63 for primary and OR=3.6 for secondary). Conclusions: Factors associated with comprehensive knowledge on HIV include: age of the woman, residence, education level, access to information and HIV response to testing. Programs designed should target young women below 19 years of age, rural women, poor women and uneducated women. Increasing campaigns to encourage more women to have HIV tests and messages using radios will increase comprehensive knowledge.