Background: The factors that influence willingness to participate (WTP) in breast cancer (BC) prevention trials are not well understood. WTP in BC prevention trials was examined in patients at increased risk of BC considering intervention and participant characteristics. Methods: Women self-identifying as being at increased risk for BC were recruited to a cross-sectional study of WTP in BC prevention trials. 78% (87 of 112) of participants completed ≥50% of a 29 item Likert Scale questionnaire about WTP in BC prevention trials that varied in intervention type and intensity, duration, time commitment, study procedures, and side effects of medications. Responses were dichotomized into “more willing” (“a lot” and “moderately”) versus “less willing” (“some,”“a little,” and “not at all”). A chi-square test was used to determine if responses differed between participants based on intervention and participant characteristics. Results: General WTP in BC ‘prevention’ studies was high at 79% “more willing”, including 67% and 72%, respectively, for unspecified physical activity and diet behavior change interventions. WTP differed significantly for diet-based behavior change interventions by type and duration; WTP was significantly lower for 12- versus 3-month interventions for both eliminating foods (28% versus 53% “more willing”, p = 0.0007) and for engaging in intermittent fasting (30% versus 45% “more willing”, p = 0.042). For physical activity, WTP decreased with duration of the intervention with 28% fewer WTP for one hour of low intensity exercise/day when compared to 30 minutes (p < 0.0001). For medications, less than half of participants (46%) expressed being “more willing” to participate, and WTP decreased significantly when possible side effects were presented (81% “less willing”) with 95% “less willing” for medications with a rare risk of serious side effects. WTP was influenced by BC risk gene mutation status, with higher proportions among gene carriers compared to non-gene carriers (59% versus 21% “more willing,” p = 0.0013), including WTP in medication chemoprevention studies (38% versus 8% “more willing,” p = 0.002). Conclusions: WTP in BC prevention trials of behavior change is high among patients at elevated risk of BC but for all women was found to be significantly negatively influenced by greater time commitment and duration of intervention beyond a few months. WTP in studies of medication is lower compared to behavior change, and very low for medications with any side effects. Overall, WTP is greater in women with known genetic risk. This study suggests that WTP may be influenced by how patients perceive their level of risk. These results also suggest that despite interest in behavior change prevention, patients may not fully recognize the relationship between sustained behavior change and potential for prevention benefit.