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Background: Initial evidence suggests Socratic questioning predicts session-to-session symptom change in cognitive behavioral therapy (CBT) for depression, but little is known about which clients are most likely to benefit from this approach. We examined pretreatment client characteristics as potential moderators of the relation between Socratic questioning and symptom improvement. Methods: Participants were 55 adults who met criteria for major depressive disorder and participated in CBT. Clients on antidepressant medication were required to be on a stable dose during the study. Therapist use of Socratic questioning was rated by trained observers at sessions 1–3 and depressive symptoms were assessed at each session. We examined four potential pre-treatment moderators of the relation of within-client Socratic questioning and session-to-session symptom change: cognitive bias, medication use, presence of a personality disorder, and dysfunctional attitudes. Results: Pessimistic bias in predicting future life events and concurrent use of antidepressant medication emerged as significant moderators with small effects. Among clients with a greater pessimistic bias and those not on antidepressant medication, Socratic questioning more strongly predicted symptom improvement. Conclusions: Findings are consistent with the view that Socratic questioning promotes session-to-session symptom improvements for some clients but plays a less important role for others. [ABSTRACT FROM AUTHOR]