Purpose <p>Despite the critical role of clinical trials in advancing cancer treatment, patient enrollment remains low at less than 10% with various health system-, provider-, and patient-level barriers [<CitationRef CitationID="CR1">1</CitationRef>]. This study explored perspectives of patients with breast cancer receiving treatment who declined clinical trial participation to work towards developing more effective, patient-centered recruitment strategies.</p> Methods <p>This qualitative study enrolled patients who were offered participation in a breast cancer clinical trial yet declined to participate from August 2023 to March 2024. Semi-structured interviews were used to elucidate patient perspectives on the clinical trial recruitment process. An open coding scheme was used to identify major themes present throughout the transcribed interviewers. Two independent reviewers then coded using NVivo 14 software with a third reviewer to settle any discrepancies.</p> Results <p>Of the 21 female patients interviewed, 43% had previously declined enrollment onto a therapeutic clinical trial and 57% a non-therapeutic clinical trial. Three core themes regarding patient-suggested strategies to optimize clinical trial recruitment emerged: (1) improving communication with patients (e.g., ensuring presentation of key information, timing of recruitment, manner of information delivery, provider involvement), (2) increasing accessibility/availability of resources to address logistical burdens (e.g., ride-share, telehealth, compensation), and (3) leveraging media in recruitment platforms.</p> Conclusions <p>This study highlights critical areas for optimization of clinical trial recruitment offering strategies such as the use of lay patient navigators, physician/researcher recruitment training in communication and implicit biases, and mixed/online recruitment. This feedback can better inform more patient centric recruitment strategies.</p>