To define whether or not the addition of anti-EGFR monoclonal antibodies to standard chemotherapy, compared with chemotherapy alone, can improve Overall Survival (OS) and Progression-Free Survival (PFS) in the patients with Metastatic Colorectal Cancer (mCRC), and evaluate the influence of KRAS mutant status on the efficacy of anti-EGFR antibodies in the first-line setting. Medline, Embase and the Cochrane controlled trials register were searched. Six trials were identified, covering a total of 4,988 subjects. A significant benefit of anti-EGFR based regimen as first-line treatment was found for OS (HR, 0.89, 95% CI: [0.80, 0.99]; P=0.04) and for PFS (HR, 0.85 [0.77, 0.94]; P=0.002) among the overall population. The PFS benefit are probably limited to KRAS wild-type patients (HR, 0.83 [0.69, 0.99] P=0.03). No significant benefit was found among KRAS-positive patients: The summary HRs was 1.13 [0.91, 1.39] (P=0.26) for PFS, 1.06 [0.94, 1.19] (P=0.34) for OS, respectively. In conclusion, our data demonstrated that the addition of anti-EFGR antibodies to chemotherapy for mCRC improved overall and progression-free survival for the overall population in the first-line setting. And the benefit from anti-EGFR antibodies as first-line treatment seems to be limited to patients with KRAS wild-type tumors with respect to PFS.