Poor enrollment into prevention trials is a major obstacle to the conduct of clinical investigations. This study focuses on cognitive and affective influences on the decision to participate in a clinical trial aimed at reducing biomarkers of breast cancer risk.Following a decision to participate or not in a clinical trial focused on reduction of breast cancer risk, women were recruited into the present study. Data were gathered via telephone survey.One hundred healthy women took part in the current study, 72 of whom had participated in the clinical trial, and 28 of whom had declined participation. Women who decided to enroll perceived more benefits and fewer costs, and they experienced more positive emotions and fewer negative emotions. They also made the decision more quickly, more easily, were more satisfied with it, and had fewer regrets than women who declined participation in the clinical trial.Participants to this clinical trial differed from nonparticipants in terms of antecedents, process, and outcomes of the decision to enroll.Although obstacles exist, accrual might be improved by greater emphasis on the practical and psychosocial benefits to participants.