PURPOSE This study assessed the short-term and long-term efficacy of a presurgical stress management intervention at reducing mood disturbance and improving quality of life (QOL) in men undergoing radical prostatectomy (RP) for prostate cancer. PATIENTS AND METHODS One hundred fifty-nine men were randomly assigned to a two-session (plus two boosters) presurgical stress management intervention (SM), a two-session (plus two boosters) supportive attention group (SA), or a standard care group (SC). Assessments occurred 1 month before surgery; 1 week before surgery; the morning of surgery; 6 weeks after surgery, and 6 and 12 months after surgery. Results Results indicated significant group differences in mood disturbance before surgery (P = .02), such that men in the SM group had significantly less mood disturbance than men in the SC group (P = .006), with no significant differences between the SM and SA or SA and SC groups. In the year after surgery, there were significant group differences on Medical Outcomes Study 36-item short form survey (SF-36) physical component summary (PCS) scores (P = .004); men in the SM group had significantly higher PCS scores than men in the SC group (P = .0009), and there were no significant differences between the SM and SA or SA and SC groups. There were no group effects on prostate-specific QOL or SF-36 mental health scores. CONCLUSION These findings demonstrate the efficacy of a brief presurgical stress management intervention in improving some short-term and long-term outcomes. If these results are replicated, it may be a useful adjunct to standard care for men with prostate cancer undergoing surgery.