Background: Self-locking stand-alone cages (MC+) and cage-with-pate fixation system are 2 different surgical methods used in anterior cervical discectomy and fusion (ACDF), but few systematic comparative studies comparing the 2 methods in treating multilevel cervical spondylotic myelopathy (MCSM) have been published. Material/Methods: Sixty-two patients with MCSM who underwent multilevel ACDF were enrolled and completed at least a 3-year postoperative follow-up. The operative time, intra-operative blood loss, and clinical and radiological results were compared between the MC+ self-locking cages group and the cage-with-plate fixation group. Clinical parameters, including VAS for neck pain, Japanese Orthopedic Association (JOA) score, and neck disabled index (NDI), were evaluated. Surgical results according to Odom's criteria and postoperative dysphagia status, C5 nerve root palsy, and loosening of the instrumentation were recorded. Postoperative radiological results, including fusion rates, fusion segmental Cobb's angle (FSC), cervical lordosis, fusion segmental height (FSH), cage subsidence, and adjacent segment degeneration, were assessed. Results: The VAS score, JOA score, and NDI score were significantly improved in both groups. However, the patients in the cage-with-plate group were more likely to have neck pain at the last follow-up. The cervical lordosis, FSC, and FSH showed significant correction immediately after surgery. The loss of the cervical lordosis and FSH were higher in the MC+ group. Conclusions: We found that use of MC+ cages is safe and effective in treating MCSM, but for patients who require strong postoperative stabilization and maintaining the cervical alignment better, the cage-with-plate fixation may best.