To evaluate the curative effect of traditional Chinese medicine(TCM) treatment focused on nourishing yin，reducing fire，relieving vexation and calming nerves on the two-year recurrence rate of major depressive disorder(MDD) with heart-kidney disharmony.Methods:Using a cohort study method，MDD patients with heart-kidney disharmony were recruited from 13 sub-centers nationwide from January 2017 to December 2018.According to the different intervention plans received by patients，they were naturally divided into traditional Chinese medicine(TCM)，integrated TCM and Western medicine，and Western medicine cohorts，and the recurrence rates among the three cohorts were compared.And according to the different intervention time of patients receiving TCM programs，the TCM and integrated TCM and Western medicine cohorts were divided into three exposure levels：low，medium，and high.The recurrence rates of the three exposure levels were compared to evaluate the efficacy of TCM programs in reducing the long-term recurrence rate of MDD with heart-kidney disharmony.Results:A total of 506 patients were included，including 172 in the TCM cohort，166 in the integrated TCM and Western medicine cohort，and 168 in the Western medicine cohort.The two-year recurrence rate was 25.6% in the TCM cohort，21.1% in the integrated TCM and Western medicine cohort，and 35.1% in the Western medicine cohort.In terms of recurrence risk，in the TCM cohort，medium exposure level was 63% lower than low exposure level（HR=0.370，95%CI 0.170 to 0.808，P<0.05），and high exposure level was 94.5% lower than low exposure level（HR=0.055，95%CI 0.016 to 0.192，P<0.01）.In the combination of TCM and Western medicine cohort，medium exposure level was 72.3% lower than low exposure level（HR=0.277，95%CI 0.111 to 0.689，P<0.01），while high exposure level was 83.9% lower than low exposure level（HR=0.161，95%CI 0.058 to 0.446，P<0.01）.Conclusion:The TCM comprehensive programme of nourishing yin，reducing fire，relieving vexation and calming nerves can effectively treat the long-term recurrence rate of MDD with heart-kidney disharmony，as well as，the recurrence rate of MDD can be gradually decreased with the intervention time of TCM.