BACKGROUND: Mindfulness-based cancer recovery (MBCR) and supportive-expressive therapy (SET) are well-validated psycho-oncological interventions, and we have previously reported health benefits of both programs. However, little is known about patients' characteristics or program preferences that may influence outcomes. Therefore, this study examined moderators of the effects of MBCR and SET on psychological well-being among breast cancer survivors. METHODS: A multi-site randomized controlled trial was conducted between 2007 and 2012 in two Canadian cities (Calgary and Vancouver). A total of 271 distressed stage I-III breast cancer survivors were randomized into MBCR, SET or a 1-day stress management seminar (SMS). Baseline measures of moderator variables included program preference, personality traits, emotional suppression, and repressive coping. Outcome measures of mood, stress symptoms, quality of life, spiritual well-being, post-traumatic growth, social support, and salivary cortisol were measured pre- and post intervention. Hierarchical regression analyses were used to assess moderator effects on outcomes. RESULTS: The most preferred program was MBCR (55%). Those who were randomized to their preference improved more over time on quality of life and spiritual well-being post-intervention regardless of the actual intervention type received. Women with greater psychological morbidity at baseline showed greater improvement in stress symptoms and quality of life if they received their preferred versus nonpreferred program. CONCLUSIONS: Patients' program preference and baseline psychological functioning, rather than personality, were predictive of program benefits. These results suggest incorporating program preference can maximize the efficacy of integrative oncology interventions, and emphasize the methodological importance of assessing and accommodating for preferences when conducting mind-body clinical trials.