Purpose <p>A qualitative focus group study was conducted to explore the perceived motivators and barriers to clinical trial participation from the perspective of women at risk for ductal carcinoma in situ (DCIS), women with a history of DCIS, and healthcare providers who care for patients with DCIS to improve recruitment to a prospective multicenter randomized prospective window of opportunity study of a tissue selective estrogen complex in postmenopausal women with DCIS.</p> Methods <p>Qualitative thematic analysis was applied to six online focus groups. The perceived motivators and barriers to participation in DCIS presurgical trials were assessed across groups. Baseline knowledge of DCIS and attitudes toward postmenopausal hormone therapies were also evaluated. Analysis was completed in NVivo.</p> Results <p>Potential DCIS pre-surgical trial participants were motivated by altruism, receiving better care, and increased monitoring by the healthcare team. Conversely, the potential for the study drug to cause harm, distrust in the medical field, and the non-life-threatening nature of DCIS were barriers to participation in pre-surgical trial. Healthcare providers felt that participants were motivated by financial incentives and receiving better care. Surgical delays, an ineffective intervention, and participant anxiety were seen as barriers to participation.</p> Conclusion <p>There was overlap in the perceived motivators and barriers to participation in a pre-surgical trial among women with a history of DCIS and at-risk women. However, healthcare providers identified differing perceived patient motivators and barriers from these groups, indicating that a greater understanding among health care providers of patient motivators and barriers may facilitate recruitment to DCIS pre-surgical trials.</p>