Findings from a survey conducted among women at high risk for HIV in Bondo, Kenya, and Pretoria, South Africa, demonstrated that a substantial proportion would be inclined to reduce their use of other HIV risk-reduction practices if they were taking pre-exposure prophylaxis (PrEP). To explore the motivations for their anticipated behavior change, we conducted qualitative interviews with 60 women whose survey responses suggested they would be more likely to reduce condom use or have sex with a new partner if they were taking PrEP compared to if they were not taking PrEP. Three interrelated themes were identified: (1) “PrEP protects”—PrEP was perceived as an effective HIV prevention method that replaced the need for condoms; (2) condoms were a source of conflict in relationships, and PrEP would provide an opportunity to resolve or avoid this conflict; and (3) having sex without a condom or having sex with a new partner was necessary for receiving material goods and financial assistance—PrEP would provide reassurance in these situations. Many believed that PrEP alone would be a sufficient HIV risk-reduction strategy. These findings suggest that participants' HIV risk-reduction intentions, if they were to use PrEP, were based predominately on their understanding of the high efficacy of PrEP and their experiences with the limitations of condoms. Enhanced counseling is needed to promote informed decision making and to ensure overall sexual health for women using PrEP for HIV prevention, particularly with respect to the prevention of pregnancy and other sexually transmitted infections when PrEP is used alone.