Study Design: This is a systematic review and meta-analysis. Objective: The aim of this study was to evaluate the efficacy and safety of multiple-level cervical disk replacement (CDR) over single-level CDR for the treatment of cervical spondylosis. Summary of Background Data: Some authors advocate for the multiple-level CDR instead of anterior decompression and fusion in cervical multiple-level spondylosis. However, whether the efficacy and safety of multi-level CDR are as favorable as that of single-level CDR remains controversial. Methods: MEDLINE, EMBASE, and Cochrane library databases were searched up to November 2015 for controlled studies that compared the clinical outcomes of single-level and multiplelevel CDR for the treatment of cervical spondylosis. The following outcomes were extracted and analyzed: prevalence of heterotopic ossification and reoperation, preoperative and postoperative Neck Disability Index scores, preoperative and postoperative Visual Analog Scale scores, and success rate using the Odom grading system. Results: Ten studies involving 1402 patients were included: including 3 randomized controlled trials, 5 prospective studies, and 3 retrospective studies. No significant differences between single-level and multiple-level groups were found in terms of the prevalence of heterotopic ossification and reoperation rate, Neck Disability Index score, Visual Analog Scale score, and success rate using the Odom grading system. Conclusions: On the basis of this meta-analysis, clinical outcomes of multiple-level CDR are similar to those of single-level CDR for cervical spondylosis, which suggests the multiple-level CDR is as effective and safe as the single-level CDR. Nonetheless, more well-designed studies are needed for further evaluation.