The objective of the study was to investigate whether acculturation to U.S. culture is associated with greater posttraumatic stress disorder (PTSD) symptomatology through diminished family cohesion among Latinos living with HIV on the U.S.-Mexico border. Baseline survey data were analyzed from a sample of Latinos seeking HIV care from a publicly funded HIV clinic in El Paso, Texas. We used a regression-based bootstrapping approach to test our mediation hypothesis. A total of 248 Latinos living with HIV completed the survey, with 96.4% being of Mexican descent, 19.4% female (gender self-identification), and 63.7% nonheterosexual (sexual orientation self-identification). Family cohesion mediated the relationship between U.S. acculturation and PTSD symptom scores (a1 ⁎ b1 = .03, 95% confidence interval [.01-.06]), an effect independent of acculturation to Latino culture. Acculturation to U.S. culture may negatively impact mental health through weakening family bonds in this vulnerable population. (PsycINFO Database Record