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Objectives: To compare five molecular targeted drugs (MTD) with interferon-α (IFN-α) and evaluate their clinical efficacy and adverse events as first line therapy for metastatic renal cell carcinoma (mRCC).Methods: We conducted a systemic review and network meta-analysis of all relevant randomized controlled trials (RCTs) assessing MTD and IFN-αthrough a comprehensive search of databases including PubMed, Science Direct,Embase and Cochrane Library databases from January 2005 to April 2014.