Background: Despite increasing awareness, racial and ethnic minorities remain under-represented in clinical trials. Understanding patients’ reasons to decline participation can help tailor solutions to improve minority enrollment in cancer trials. Methods: Parkland Health (Dallas County, TX) is a safety-net health system, and affiliated with the UT Southwestern/Harold C. Simmons Comprehensive Cancer Center (SCCC). Over 80% of the breast cancer patients treated at Parkland belong to racial and ethnic minorities. Potential study candidates are referred to the clinical trial support team, which includes a Hispanic bilingual patient navigator. Patients who decline to participate are asked to describe their reasons. Data for screening and accrual to therapeutic breast cancer trials at Parkland between January 2021 and May 2022 is presented here. Results: A total of 193 potential study candidates were referred to the trial support team in the pre-screening phase. Ninety-five patients (49%) were excluded after screening (screen-fails). Of the 98 patients who met all study specific eligibility criteria, 93% belonged to minorities: 69% (68/98) Hispanics and 23% (23/98) Blacks. Thirty-one patients (32%) declined participation in clinical trials. Compared to Hispanics, Black patients were more likely to decline participation: Blacks 65% (15/23) vs Hispanics 19% (13/68); p < 0.0001. Patients' reasons for declining to participate in trials included: lack of interest (14/31), excessive trial requirements such as extra biopsies (8/31), and potential delay in treatment due to additional tests (5/31). Four patients declined participation in a de-escalation trial due to the fear of inferior outcomes with less treatment. Among patients who declined participation, 53% of Blacks and 23% of Hispanics cited lack of interest as the reason (p = NS). Conclusions: We observed a higher participation rate among Hispanics, which may in part reflect the impact of having a bilingual research navigator from the same ethnic background. Lack of interest was a major reason to decline, particularly among Blacks. Strategies focused on patient education and trust are being implemented to further improve minority participation in trials at our institution.