Background: Trichomonas vaginalis (T. vaginalis) is the most common nonviral sexually transmitted infection in the world. Despite the coexisting global epidemics of T. vaginalis and HIV, little attention has focused on the emerging evidence that T. vaginalis increases susceptibility to, and potentially transmission of, HIV. Methods: We evaluated T. vaginalis infection in the context of a multisite, randomized controlled trial amongst women in South Africa and Zimbabwe, to determine first, if risk of HIV acquisition was increased among women recently infected with T. vaginalis, and second, if risk of T. vaginalis acquisition was increased among women infected with HIV. Results: After controlling for potential confounders, participants infected with T. vaginalis were more likely to test positive for HIV at their following visit, compared to participants uninfected with T. vaginalis (adjusted hazard ratio = 2.05; 95% CI, 1.05-4.02). Similarly, HIV-positive participants were twice as likely to have acquired T. vaginalis infection at the following visit, compared to HIV-negative participants (adjusted hazard ratio = 2.12; 95% CI, 1.35-3.32). Conclusions: We found an increased risk of both HIV acquisition associated with T. vaginalis infection and risk of T. vaginalis acquisition associated with HIV infection. This bidirectional relationship represents a potentially important factor in sustaining the HIV epidemic in populations where T. vaginalis is endemic. Copyright © 2010 American Sexually Transmitted Diseases Association. All rights reserved.