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A meta-analysis of randomized controlled trials (RCT) was carried out to determine the efficacy and safety of capecitabine plus oxaliplatin (CAPOX) or fluorouracil plus oxaliplatin (FUOX) as first-line treatment for metastatic colorectal cancer (MCRC).A literature search was conducted of the Cochrane Controlled Trials Register Databases, Medline, Embase, ISI databases and Chinese Biomedical Literature Database without exclusion of material published in any language. RCTs conducted between 1998 and 2008 of CAPOX compared with FUOX regimens were considered for inclusion. Statistical analyses were carried out using RevMan software.Ten RCTs were included, involving 3208 patients. The meta-analysis showed that there were no statistically significant differences in tumour response rate (RR, 0.93; 95% CI, 0.87–1.01; P = 0.09), progression-free survival (PFS) (RR, 0.98; 95% CI, 0.94–1.01; P = 0.19), and overall survival (OS) (RR, 1.02; 95% CI, 0.97–1.07; P = 0.47) between CAPOX and FUOX regimen. However, symptoms of thrombocytopenia and hand-foot syndrome (HFS) were increased in the CAPOX regimen (RR, 1.89; 95% CI, 1.33–2.69; P = 0.0004 and RR, 3.40; 95% CI, 2.25–5.15; P < 0.00001 respectively), while neutropenia and leucopenia occurred more frequently in the FUOX regimen (RR, 0.29; 95% CI, 0.15–0.55; P = 0.0002 and RR, 0.41; 95% CI, 0.18–0.95; P = 0.04respectively).CAPOX was equivalent to FUOX in terms of tumour response rate, progression-free survival (PFS), and OS in first-line treatment for patients with MCRC, which may be considered as standard first-line treatment in patients with MCRC.