Introduction: Depression is one of the most important psychiatric disorders, and the rate of recurrence is high. The heavy cost burden of depression is probably due to treatment-resistant depression. The purpose of this study was to determine the effectiveness of mindfulness-based cognitive therapy (MBCT) in patients with treatment-resistant depression (TRD). Method: The present study was a quasi-experimental study conducted with twenty-four patients with treatment-resistant depression. Participants were selected by purposive sampling and randomly assigned to two groups, an experimental group and a control group. The experimental group received MBCT and antidepressants, while the control group received antidepressants only. The Hamilton and Beck Depression Inventory, Self-Compassion Scale, Thought Rumination Scale, and Mindfulness Scale were administered. The treatment program was conducted in eight sessions; with a follow-up period of one month subsequent to treatment termination. Data were analyzed using descriptive statistics (mean and standard deviation) and inferential statistics (analysis of variance for repeated measures and Bonferroni’s post-hoc test). Results: The results showed that MBCT significantly reduced depression and ruminative thinking in the experimental group and also improved mediators such as mindfulness and self-compassion. Patients maintained gains over the one month follow-up period (p < 0.01). Conclusion: The present study provides additional evidence for the effectiveness of MBCT for TRD.