Objective：To access the efficacy and safety of Tianeptine versus selective serotonin reuptake inhibitor（SSRI） in the treatment of depression. Methods：Randomized controlled trials（RCTs） in relevant databases：Cochrane Library，PubMed，Web of Knowl－edge，Embase，China Biology Medicine Literature，China National Knowledge Internet，Wanfang Data and VIP were searched. Quality of the included literature was evaluated and data were extracted. Review Manager 5.2 software was used for Meta analysis. Results：Twelve RCTs of 2 143 patients were included in our study，1 086 patients in Tianeptine group and 1 057 patients in SSRI group. Meta-analysis results indicated that there was no difference in efficiency between Tianeptine group and SSRI group（effective rate RR=1.01，95%CI=0.95 to 1.07，P=0.85）. Incidences of nausea，vomiting，constipation，insomnia and loss of appetite were significantly lower in Tianeptine group than in SSRI group（P<0.05） while incidence of somnolence was higher in Tianeptine group than in SSRI group. There was no statistical difference in other side effects between the two groups（P >0.05）. Conclusion：Although no statistical difference is observed in the efficacy between Tianeptine and SSRI，however，Tianeptine induces fewer side reactions，there of clinical guiding significance.