Abstract Background: Eliminating racially driven cancer inequities requires conducting research with underrepresented groups, such as Black Americans, yet research participation is not comparable with the burden of cancer in this population. Distrust of the healthcare system is often cited as a central reason for Blacks' lower cancer research participation rates. Few studies have explored whether distrust operates alone or in combination with other attitudes toward research to influence Blacks' intention to participate in cancer research. The study purpose was to explain the relationship between healthcare distrust and the intention to participate in cancer prevention research among a group of Southern Blacks. We hypothesized that healthcare distrust would be inversely related to and a significant predictor of intention to participate in cancer prevention research. Methods: A survey tool was developed based on previous qualitative research and administered between November 2014 and July 2015. Eligible respondents identified as Black American, were 18 or older, residents of South Carolina, and had never been diagnosed with cancer. Of the 208 surveys collected, 194 met eligibility criteria. Analyses were restricted to 130 participants with complete responses. Survey items assessed participant demographics, healthcare distrust, and previous research participation. Research related attitudes/beliefs collected included positive and negative beliefs about research participation, social norms around participation, and beliefs about individual and community level outcomes of research participation. Multiple regression models were created to describe the relationship between negative beliefs about cancer prevention research and intention to participate in cancer prevention research. Analyses were conducted in STATA 13. Results: The analytic sample was predominately female (88.5%), employed (73.9%), lived in urban areas (83.9%), and had a high school education or less (55.4%). A large proportion reported being likely or very likely to participate in cancer prevention research (83.4%) but only 34.6% reported previous participation in health research. Intention to participate in cancer prevention research had a slightly negative association with healthcare mistrust (r= -0.19). Healthcare mistrust was predictive of intention to participate in the base model (R2=0.04), but after the addition of control variables healthcare mistrust became an insignificant predictor. The model was strengthened with the addition of scales reflecting positive and negative attitudes, social norms, and outcomes related to cancer prevention research participation (R2=0.40). Except for participation outcomes, all research related beliefs were significant predictors of intention. Additional models were constructed to determine the demographic covariates of research related beliefs. Only the model describing social norms around cancer prevention research was significant (R2=0.17), with gender serving as a significant predictor of the model. Conclusion: Although commonly referenced as a barrier to research participation among Black Americans, healthcare distrust failed to predict intention to participate in cancer prevention research. Social norms regarding participation and positive and negative attitudes toward participation in cancer prevention research were strong predictors of intention, yet beliefs about the outcomes of research had no impact on willingness to participate. This study highlights the need to explore a wider set of attitudes and beliefs in order to determine what drives intention to participate in cancer research in this population. Equally important is the need to explore influences on research participation outside of intention given the disparity between intention and participation in the study sample. Citation Format: Deeonna E. Farr, Heather M. Brandt, Daniela B. Friedman, Cheryl A. Armstead, Sue P. Heiney, Swann A. Adams, Wanda Green, Samira Khan, James R. Hebert. Untangling the influence of healthcare distrust on black Americans' intention to participate in cancer prevention research. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C03.