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Introduction: Different types of psychotherapy are effective for treating major depressive disorder across groups yet show large within-group differences. Patient personality style is considered a potentially useful variable for treatment matching. Objective: This study is the first experimental test of the interaction between therapeutic approach and patients' dependent versus self-critical personality styles. Methods: A pragmatic stratified parallel trial was carried out with 100 adult patients diagnosed with DSM-IV-TR major depressive disorder. They were randomly assigned to short-term (16–20 sessions) cognitive behavioral therapy (CBT) or short-term psychodynamic psychotherapy (STPP). Patients were assessed at baseline, during therapy, post-therapy, and at 3- and 6-month follow-up. Primary outcome is depression severity measured by the Hamilton Rating Scale for Depression posttreatment. Primary analysis was by intention to treat. This trial is registered with the ISRCTN registry (www.isrctn.com), number ISRCTN17130982. Results: The intention-to-treat sample consisted of 100 participants; 40 with self-critical and 60 with dependent personality styles were randomized to either CBT (n = 50) or STPP (n = 50). We observed no interaction effect (−0.34 [−6.14, 5.46]) between therapy and personality style and found no evidence for a difference in effectiveness between the treatments in general in terms of symptom reduction and maintained benefits at 6-month follow-up. Conclusion: We found no evidence that dependent versus self-critical personality styles moderate the relation between treatment and outcome in depression. Research using individual patient data could gain further insight into why specific therapeutic approaches work better for specific patients. [ABSTRACT FROM AUTHOR]