Introduction: The aim of this study was to investigate the efficacy of metacognitive therapy (MCT) on improvement of symptoms of major depression, cognitive attentional syndrome, and maladaptive copings in two patients with major depression. Case Description: In a single case experiment with multiple baseline design 2 women suffering from major depressive disorder (MDD) were treated with eighth weekly sessions of MCT and antidepressant medications. Instruments used in this research were included Beck depression inventory, major depressive disorder scale (MDD-S), metacognitive beliefs, metacognitions questionnaires, ruminative response style (RRS), and cognitive attentional syndrome (CAS) scale. Results: Data indicated that metacognitive treatment resulted in reduction of subject's scores in metacognitive scale and RRS scale in post-test and 2 months follow up. The CAS and MDD-S scores showed remarkable reduction. Conclusion: Metacognitive therapy as a new emerging approach appears to be an effective treatment approach for patients suffering from MDD. The effect of MCT can be due to decrease in rumination and/or positive and negative metacognitive beliefs.