Abstract Background: Biannually, Sidney Kimmel Cancer Center at Jefferson in Philadelphia, PA their catchment area to identify and describe the population. Since less than 6.3% of cancer patients nationally are involved in clinical trials, the most recent survey included questions related to willingness to participate in clinical trials (CTs) and reasons for or against participation. Methods: A cross-sectional study was conducted among adult residents in Philadelphia, Delaware, Bucks, and Montgomery Counties in Pennsylvania as well as Camden, Burlington, and Gloucester Counties in New Jersey from July to August 2022 and included 2,744 respondents. Survey questions included reasons for or against willingness to participate in CTs, lifestyle behaviors, cancer screening frequencies, cancer attitudes or beliefs, health literacy, and numeracy. Frequency counts were weighted against population totals from the American Community Survey. The survey was fielded in English, Spanish, and Chinese. The univariate associations of covariates with the outcome were evaluated with a ꭓ2 test. Logistic regression using weighted survey procedures were used to calculate the odds ratios (ORs), 95% confidence intervals (CIs), and p-values of trial participation controlling for covariates. Results: The weighted sample represented the 3,889,048 residents of the catchment area. Survey respondents completed the survey in English (80.1%), Spanish (13.2%), and Chinese (6.7%) and self-identified as Hispanic (9.3%), non-Hispanic (NH) White (57.8%), NH Black (19.0%), and NH Other (14.0%). The catchment population was willing to participate in CTs (69.8%). Respondents answering in Chinese were 40% less likely than those answering in English to indicate future CT participation (OR 0.60, p=0.04). Both Hispanic and NH Black respondents were over 30% less likely to participate compared to NH Whites (OR 0.67, p=0.03 and 0.68 p=0.02, respectively). While some respondents view CTs as “experiments” (17.0%), the most common reason given not to participate in a CT was side effects (25.6%). Respondents reporting a high level of discrimination were 48% more likely to participate in a CT than low discrimination respondents (p=0.02). The population reporting the highest level of discrimination also reported wanting to participate to “learn more about their health and medical condition” (66.3%) and a desire to “help my community” (54.5%). Conclusions: Clinical trials offer a segment of the population access to care not normally available and a way to serve their community. However, fear of experimentation remains a strong reason not to participate. The findings highlight the importance of catchment assessment when designing recruitment methods and future endeavors involving education on the trial safety of trials may improve participation. While education may assuage fears, it will not dispel mistrust. Proactively engaging the community in study design may help repair the relationship between science and the people it serves. Citation Format: Amy L. Shaver, Nikita Nikita, Joshua Banks, Christiane El Khoury, Rebecca J. Melillo, Yawei Song, Grace Lu-Yao, Amy E. Leader. Factors associated with willingness to participate in future clinical trials [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A082.