The factors affecting women's willingness to participate (WTP) in breast cancer (BC) prevention trials are poorly understood. This study aimed to identify the characteristics of interventions associated with a higher WTP among high BC risk women. Women who self-identified as being at an increased risk of BC were recruited to a cross-sectional study of WTP in BC prevention trials. Responses were dichotomized into more willing (a lot and moderately) and less willing (some, a little, and not at all), and responses were compared by patient characteristics and intervention type. Of 143 participants, 81.2% (116) completed ≥30% of a Likert-type scale questionnaire on WTP in various intervention types for BC prevention. Overall, WTP in BC prevention studies was high, with 82.7% more willing, including 69.0% and 70.7%, respectively, for unspecified physical activity and dietary interventions. WTP differed significantly by the duration of diet-based and physical activity behavior change interventions: decreasing with 12- versus 3-month diet-based interventions (P < .0001) and decreasing for 1 hour versus 30 minutes of low-intensity exercise/day (P < .0001). For interventions involving medication, only 18.1% expressed being more willing to participate, and WTP decreased significantly when side effects were presented. WTP was influenced by BC risk gene mutation status, with WTP among gene carriers higher compared with nongene carriers (52.6% v 30.2%, P = .018). WTP in BC prevention trials was the highest for women with known genetic risk and for interventions involving a behavior change. Medications with side effects had the lowest WTP. For behavior change, WTP was negatively influenced by intervention duration beyond a few months, indicating that individual perception of BC risk and inconvenience strongly influence WTP.