Existent research reveals that inequitable gender-based power in relationships and intimate partner violence contribute to HIV rates among women in the developing world. This study uses a multi-country analysis to examine women’s autonomy in negotiating safe sex practices such as having sex with a partner with no other concurrent partner to reduce the risk of HIV/AIDS in Nigeria, Kenya, Malawi, and Nepal. The Demographic Health Survey data for Nigeria (2013), Kenya (2008–2009), Malawi (2010), and Nepal (2011) provide geographical variability as well as HIV risk variables. The sample included 16,540 women aged 15–49 years who self-identified as ever married. Factor analysis for women’s autonomy was conducted based on socio-cultural theory. Logistic regression was conducted and results identified decision-making, labor force participation, and individual autonomy as women autonomy factors significantly reduced the risk for HIV infection by having one sex partner who has only one sex partner. Other women autonomy factors related to lower risk for HIV include education, place of residence, and religion. Our study indicates that effective management of HIV transmission requires addressing women autonomy factors within the context of culture.