Abstract: OBJECTIVE To systematically evaluate the adverse reactions of cephradine and its control drugs in the treatment of infection. METHODS CNKI, Wangfang, VIP, Sinomed, PubMed, Embase and Cochrane Library database were searched by two researchers and randomized controlled trials(RCTs) about the safety of cephradine in clinical application for infection were retrieved according to inclusion and exclusion criteria. The eligible RCTs were given meta analysis by using the statistical software RevMan 5.3 and the trial sequential analysis(TSA) software performs test sequence analysis. RESULTS Totally 50 RCTs with 7 477 cases were included in this study. The results of meta-analysis and TSA were as follows:①there were statistical differences in the incidence of adverse reaction between cephradine groups and control groupRR=0.62, 95%CI(0.54, 0.72), P<0.000 01. ②Respiratory infection subgroup analysis showed that there were statistical differences in the incidence of adverse reaction between two groupsRR=0.66, 95%CI(0.53, 0.80), P<0.000 1, sample size of other indications was too small to be analyzed. ③The subgroup analysis of control drugs indicated that the incidence of adverse reaction in cefradine group was higher than azithromycin, cefixime and cefaclor group, but lower than amoxicillin/clavulanic acid group, only azithromycin group showed statistical differencesRR=0.44, 95%CI(0.28, 0.70), P=0.000 5, and the TSA result showed that the evidence was definite. ④The subgroup analysis of drug does showed that there were statistical difference in over dosage groupRR=0.70, 95%CI(0.54, 0.91), P=0.008 and routine dosage groupRR=0.61, 95%CI(0.52, 0.71), P ≤ 0.000 01. CONCLUSION The incidence of cephradine adverse reaction is significantly higher than other group. It is necessary to be cautious in the occurrence of adverse reactions and strictly follow the instructions.