Objective To systematically evaluate the efficacy of clozapine combined with other antipsychotic drugs in the treatment of refractory schizophrenia. Methods We searched Medline, EMBASE, and China Biology Medicine databases in both English and Chinese for randomized controlled trials, quasi-randomization controlled trials, and clinical controlled trials concerning the combinations of clozapine with other antipsychotic drugs for refractory schizophrenia. Quality assessment and data extraction were conducted with the Cochrane collaboration's RevMan 5.3 software. Results Totally 47 trials met the inclusion criteria, in which clozapine was combined with risperidone, aripiprazole, sulpiride, ziprasidone, modified electroconvulsive therapy, valproate, or lithium carbonate, respectively. Analysis showed that most combination strategies were superior to clozapoine alone (P<0.05), except for the combination with lithium carbonate(8 weeks: RR=1.27, 95%CI=0.82-1.97,P=0.28; 12 weeks: RR=1.53, 95% CI=0.45-5.13, P=0.49). Conclusion Reasonable combination of clozapine with other drugs may improve the therapeutic effectiveness and reduce adverse reactions and thus can be effectively used for treating refractory schizophrenia.