The current study assessed the efficacy of a brief video intervention (Prevention of Post-Rape Stress [PPRS]) delivered in the emergency department to recent sexual assault (SA) victims. PPRS was compared to treatment as usual (TAU) and an active control condition (Pleasant Imagery and Relaxation Instruction [PIRI]). Primary outcomes were posttraumatic stress disorder (PTSD) symptoms and perceived present control. Prior SA was examined as a moderator of treatment effects. Women ( n = 233; aged 15 years and older; 59.70% identified as a racial or ethnic minority) who received a post-SA medical forensic exam participated in the study (NCT01430624). Participants were randomized to watch the PPRS video ( n = 77), the PIRI video ( n = 77), or receive TAU ( n = 79). Participants completed measures of PTSD symptoms and perceived present control 1.5-, 3-, and 6-months post-SA. An interaction between condition and prior SA was found on PTSD symptom frequency and on perceived present control. Among women with a prior SA, women in the PPRS versus TAU condition reported less frequent PTSD symptoms 6-months post-SA. Those in the PPRS condition had lower perceived present control than those in the TAU condition among those with no prior SA 3-months post-SA. However, at 6-months post-SA, among women with a prior SA, women in the PPRS reported higher perceived present control than those in TAU. These findings partially replicate a prior study in which PPRS was found to be beneficial in mitigating the development of PTSD symptoms, but only for women with a prior SA.