In Ethiopia the level of illiteracy in rural areas is very high. In this study, we investigated the effects of an audio HIV/AIDS prevention intervention targeted at rural illiterate females. In the intervention we used social-oriented presentation formats, such as discussion between similar females and role-play. In a pretest and posttest experimental study with an intervention group (n = 210) and control group (n = 210), we investigated the effects on HIV/AIDS knowledge and social cognitions. The intervention led to significant and relevant increases in HIV/AIDS knowledge, self-efficacy, perceived vulnerability to HIV/AIDS infection, response efficacy of condoms and condom use intention. In the intervention group, self-efficacy at posttest was the main determinant of condom use intention, with also a significant contribution of vulnerability. We conclude that audio HIV/AIDS prevention interventions can play an important role in empowering rural illiterate females in the prevention of HIV/AIDS.