OBJECTIVE:To systematically evaluate therapeutic efficacy and safety of Toutongning combined with flunarizine vs. flunarizine in the treatment of migraine,and to provide evidence-based reference in clinic. METHODS:Retrieved from PubMed,Cochrane library,Embase,Chinese Journal Full-text Database,Chinese Sci-tech Periodicals Database,Wanfang database and CBM,randomized controlled trials(RCTs)about therapeutic efficacy(total response rate,VAS score,blood potassium and blood magnesium concentration,CGRP level)and safety(the incidence of ADR)of Toutongning combined with flunarizine(trial group)vs. flunarizine in the treatment of migraine(control group)were collected. Meta-analysis of included trials meet inclusion criteria was conducted by using Stata 14.0 software,and trial sequential analysis(TSA)was conducted by using TSA 0.9 software after data extraction and quality evaluation with Cochrane 5.1.0 bias risk evaluation tool and Jadad scale. RESULTS:Totally 16 RCTs were included,involving 1 726 patients. Results of Meta-analysis showed that total response rate [RR=1.21,95%CI(1.16, 1.26),P<0.05],the decrease of VAS score [WMD=-1.04,95%CI(-1.42,-0.66),P<0.001],the decrease of blood potassium [WMD=-2.05,95%CI(-0.32,-0.18),P<0.001],the increase of blood magnesium [WMD=0.09,95%CI(0.04,0.14),P<0.001] and the decrease of CGRP [WMD=-2.22,95%CI(-3.25,-1.18),P<0.001] in trial group were better than control group,with statistical significance. The incidence of ADR in trial group was 2.27% in trial group and 2.89% in control group, without statistical significance(P>0.05). TSA showed that there were extract evidences for total response rate of Toutongning combined with flunarizine in the treatment migraine. CONCLUSIONS:Therapeutic efficacy of Toutongning combined with flunarizine is better than flunarizine in the treatment of migraine,and the ADR is not increased.