Background: In this studyMindfulness and CBT were combined to investigate the enhance of psychotropic work. Both therapies have integrated acceptance-based mindfulness approaches with change-based cognitive behavioral therapies to create efficacious treatments. That is, introduce use of MBCT in active phase of treatment and chronic depression.Objectives: This study was done to evaluate efficacy of Mindfulness Based Cognitive Therapy (MBCT) and traditional Cognitive Behavior Therapy (CBT) with Treatments as usual (TAU) to reduce psychiatric symptoms in a sample of patients with Major Depressive Disorder (MDD). Materials and Methods: 90 patients who were referred to clinics of university of Social Welfare and Rehabilitation Sciences and Tehran University Counseling Centre and met DSM-IV criteria for MDD were selected. They were randomly assigned to MBCT (n = 30), CBT (n = 30), or TAU (n = 30). They were aged between 18 and 45 years (M = 28, SD = 8), with an average of two previous depression episodes. They were interviewed through the Structured Clinical Interview for DSM-IV and self-report by Brief Symptom Inventory, pre and post treatment. Patients in MBCT and CBT group received the treatment, while TAU group continued therapy (anti-depressant). Results: The results indicated that MBCT and CBT groups have significant efficacy on reduction of MDD symptoms. Conclusions: MBCT appears to be as effective as CBT in the treatment of current depression.