OBJECTIVE: To conduct a comprehensive PRISMA-compliant systematic review and Meta-analysis to evaluate the safety and efficacy of genotype-guided initial dosing of warfarin. METHODS: PubMed, Web of Science, Cochrane library, CNKI, CBM, and Wanfang data were electronically searched, and randomized controlled trials comparing pharmacogenetic dosing of warfarin vursus routine anticoagulant treatment were included. Then two reviewers independently used EndNote X7 software to filter the literatures, extracte data and assess study quality, and Revman 5, 2 software was used to conduct Meta analysis, The primary endpoints were the percentage of time within the therapeutic INR range and adverse events, The secondary endpoints were the time to reach a stable warfarin dose and the propotion of patients reaching stable warfarin dose. RESULTS: Nine trials met the inclusion criteria, in which a total of 1390 patients were randomly assigned to genotype-guided group and control group (traditional dosing) to receive warfarin treatment with a follow-up time ranging from 4 weeks to 3 months, It was discovered that the percentage of time within the therapeutic INR range in genotype-guided group was improved compared with the control group when the initial routine dose was fixed [SMD=0.26, 95% CI (0.11, 0.41), P=0.0006], and a smaller number of patients in genotype-guided group developed adverse events [RR=0.75, 95% CI (0.66, 0.84), P<0.00001], Genotype-guided group reached stable warfarin dose earlier compared with the control group [SMD=-3.49, 95% CI (-6.15, -0.84), P=0.01], but there was statistical heterogeneity among the studies (P<0.00001, I2=99%), The propotion of patients who reached stable dose in genotype-guide group was larger than that in traditional dosing group [RR=1.25, 95% CI (1.15, 1.35), P <0.00001], CONCLUSION: Genotype-guided initial dosing of warfarin can increase the percentage of time within the therapeutic INR range, reduce the incidance of adverse events, shorten the time to reach stable dose, and increase the propotion of patients reaching stable dose.