OBJECTIVES: Understanding determinants through which healthcare interventions influence health outcomes may highlight ways in which it can be maximized. This study explores the role of pre-treatment credibility and expectancy on the outcome of depression treatments in primary care. METHODS: Data are used of a randomized trial comparing 1) computerized cognitive behavioral therapy for depression (CCBT); with 2) treatment as usual by a general practitioner (TAU); and 3) a combination of both. Credibility and expectancy were assessed after treatment allocation prior to treatment, with an adjusted and translated version of the Credibility and Expectancy Questionnaire. Moderators of expectancy and credibility are explored in a backward linear regression analysis. The contribution of credibility and expectancy to the severity of depression (BDI-II) and the quality-of-life (SF-6D) outcome at 12 months after baseline is explored in a stepwise linear regression, controlling for baseline depression severity, baseline quality-of-life, sex, and age. RESULTS: The type of intervention and educational level contribute to the level of pre-treatment expectancy and credibility. No significant association with credibility or expectancy was found for sex, age, partner, employment status, baseline quality-of-life, baseline severity of depression, and the presence of previous depressive episodes during lifetime. In the CCBT and the TAU groups, pre-treatment expectancy was associated with the depression severity outcome, while credibility was significant for this outcome in TAU and tends towards significance in the CCBT group. For quality-of-life, only the expectancy factor contributed to the outcome in CCBT, and both credibility and expectancy tend towards significance in the TAU group. Credibility and expectancy do not contribute to the outcomes of the combined treatment. CONCLUSIONS: Patients’ initial belief about the success of their depression treatment can influence the outcome. Taking the patient’s pre-treatment expectancy and credibility into account may contribute to a more effective treatment.