BACKGROUND: Major depressive disorder (MDD) is the important cause of disability in the world. Major depressive patients that are not respond to the first and second drugs are about 67% and 33%, respectively. Therefore the effective treatment is urgently needed. OBJECTIVE: To examine the effect of Buddhist mindfulness meditation combined with standard treatment on depression and quality of life in major depressive patient compared to the control group. MATERIAL AND METHOD: It was a quasi experimental study. The subjects with age ranged 20-70 years old and had Thai Hamilton rating scale for depression 13-29 scores were divided in two groups, each group contained 30 persons. The intervention was Buddhist mindfulness meditation which meditated everyday at least 5 days/week, 15 minutes each time, for six weeks. Both groups were treated with standard treatment. All subjects were tested using Thai Hamilton rating scale for depression, and WHOQOL-BREF-THAI questionnaire at baseline and every week for six weeks. Compare the result of Buddhist mindfulness meditation by independent t-test and Chi-square. RESULTS: The difference between the average of Thai Hamilton rating scale for depression (17.33+5.22 in meditation group and 17.67+6.33 in control group) and WHOQOL-BREF-THAI questionnaire (29.97+15.95 in meditation group and 31.33+12.12 in control group) before and after meditation was not statistically significantly among the two groups (p>0.05). However, it found that at the 6th week, 28 patients from the meditation group (93.3%) and 22 patients (73.3%) from the nonmeditating group improved from depression. When examining by the Chi-square, the meditating group had a statistically significantly different in the number of patients that improved from depression (p-value = 0.04). CONCLUSION: At the 6th week of Buddhist mindfulness meditation, significant number of patients were improved from depression. Thus, Buddhist mindfulness meditation should be included in the treatment of depression.