OBJECTIVE: This meta-analysis was conducted to evaluate the therapeutic effects in clinical and radiologic outcomes of a self-locking stand-alone cage (SSC) and cage-with-plate (CP) for multilevel anterior cervical discectomy and fusion (ACDF). METHODS: A systematic search was performed for all comparative studies reported up to August 2018. Operative time, hospital stay, intraoperative blood loss, Japanese Orthopedic Association score, Neck Disability Index (NDI), cervical and segmental Cobb angle, intervertebral height, fusion rate, incidence of subsidence, dysphagia, and adjacent segment degeneration were analyzed with the RevMan 5.3.3 software. RESULTS: A total of 15 studies were included. There was no difference regarding preoperative or postoperative Japanese Orthopedic Association score, Neck Disability Index, segmental Cobb angle and intervertebral height, preoperative cervical Cobb angle, fusion rate, incidence of subsidence, and adjacent segment degeneration between the SSC and CP group (P > 0.05). However, the SSC group had shorter operative time (mean difference [MD], -11.35; 95% confidence interval [CI], -16.24 to -3.66) and hospital stay (MD, -0.64; 95% CI, -1.21 to -0.06), less intraoperative blood loss (MD, -13.22; 95% CI, -19.03 to -7.41) and postoperative cervical Cobb angle (MD, -0.70; 95% CI, -1.35 to -0.06), and lower incidence of dysphagia significantly (odds ratio, -0.57; 95% CI, 0.40-0.82) (P < 0.05). CONCLUSIONS: ACDF with SSC and CP in multilevel cervical spondylosis achieved similar clinical relief. Although CP maintained better cervical lordosis, SSC contributed to less surgical pain and fewer complications. ACDF with SSC is safe and efficient in treating multilevel cervical spondylosis.