Background: Concurrent chemoradiotherapy (CTRT) or RT + cetuximab (RT + CET) are both treatment options for the treatment of locally advanced head and neck cancer (HNC). The efficacy of these two treatment modalities for patients with locoregionally advanced or inoperable HNC however has never been compared. Methods: We conducted a systematic review and meta-analysis by searching in PubMED, EMBASE, SCOPUS, Web of Science and The Cochrane Register of Controlled Trials, to compare CTRT and RT + CET in locally advanced HNC. Risk ratios (RRs) with 95% confidence intervals (95%CIs) were calculated for pre-specified endpoints as 2-year overall survival (OS), 2-year disease free-survival (DFS), 2-year loco-regional relapse (LRR) and 2-year distant metastases (DM). Meta-analysis was performed using the fixed- or random-effects models. Results: 15 trials for a total of 1,808 patients, were included. Concurrent CTRT significantly improved 2-year OS (RR=0.66, 95% CI 0.46-0.94; P=0.02), 2-year DFS (RR=0.68, 95% CI 0.53-0.87; P=0.002) and 2-year LRR (RR=0.63, 95% CI 0.45-0.87; P=0.005) compared to RT + CET. The absolute risk differences were 12%, 17% and 10%. Risk of distant metastases was identical (RR=1.01, 95%CI 0.69-1.48; P=0.94). Conclusions: Platinum-based CTRT is associated with a better 2-year OS and locoregional control compared to RT + CET, and still remains the standard of care in locally advanced HNC until prospective trials can demonstrate equivalence.