OBJECTIVE To compare the efficacy and safety of doxorubicin with epirubicin in patients with metastatic breast cancer (MBC) by systematic review and Meta-analysis to provide reference for clinicians. METHODS Randomized controlled trials (RCTs) that compared the efficacy, safety, or both, of doxorubicin with epirubicin in treatment of metastatic breast cancer were collected from the Cochrane library, PubMed, Embase, CNKI, CBM and Wanfang database using the following terms: doxorubicin, epirubicin, breast cancer, randomized controlled trials. In addition, the reference lists of relevant trials or reviews were screened. Trials that provided sufficient data onOBJECTIVE response rate (ORR) and/or overall survival (OS) were considered eligible for inclusion. Studies were assessed for quality. A fixed-effect model was used for Meta-analysis unless there was significant between-study heterogeneity. Meta-analysis was performed by Revman 5.3 software, with RESULTS expressed as odds ratio (OR), 95% confidence interval (CI) and P value. The other parameters were summarized by descriptive analysis. RESULTS A total of 1 221 patients from six RCTs were included for final analysis, with 614 patients in the doxorubicin group and 607 patients in the epirubicin group. The median OS was 549 d for the doxorubicin group and 480 d for the epirubicin group. The pooled risk ratio(RR) suggested that there was not statistically significant difference in the ORRs between the doxorubicin (general type and liposomal type) group and the epirubicin group for the treatment of MBC [for doxorubicin vs epirubicin, RR=1.12, 95% CI(0.99,1.26), P=0.07; for liposomal doxorubicin vs epirubicin, RR=1.24, 95% CI(0.94,1.62), P=0.12]; and for general doxorubicin vs epirubicin RR=1.09, 95% CI(0.96,1.24), P=0.12).Descriptive analysis of safety showed that doxorubicin had similar incidences of hematologic toxicity and alopecia to epirubicin but was superior to epirubicin in aspect of cardiac toxicity. There was no significant heterogeneity among the included studies in most of the Meta-analyses. CONCLUSION Epirubicin and doxorubicin are equally effective and the safety profile of the former is at least not worse than the latter in the first-line treatment of patients with metastatic breast cancer. But compared to doxorubicin, epirubicin might be a better choice for MBC patients especially those with cardiac diseases.