Although the Food and Drug Administration (FDA) approved oral Truvada for pre-exposure prophylaxis (PrEP) for women at risk of HIV infection in the US in July 2012, and the Centers for Disease Control and Prevention (CDC) issued guidance for clinicians to provide PrEP to women "at substantial risk of HIV acquisition" in May 2014, there remain no clinical trial data on efficacy among US women, and there is a dearth of research on knowledge, attitudes, and likelihood of use of PrEP among them. We conducted a qualitative focus group (FG) study with 144 at-risk women in six US cities between July and September 2013, including locations in the Southern US, where HIV infections among women are most prevalent. FG questions elicited awareness of PrEP, attitudes about administration and uptake, and barriers to and facilitators of use. Women expressed anger at the fact that they had not heard of PrEP prior to the study, but once informed most found it attractive. PrEP was seen as additional, not substitute protection to condoms, and participants suggested several dissemination strategies to meet the diverse needs of women. Key barriers to PrEP uptake included distrust of the medical system, stigma, and cost. Findings suggest that US women view PrEP as an important prevention option, assuming side effects and the cost to the consumer are minimal, the efficacy of the drug is reasonable, and PrEP is delivered by trusted providers in trusted venues.