Objective: To compare the medium-term clinical and radiologic outcomes between anterior decompression with fusion (ADF) and posterior open-door laminoplasty (LAMP) in the treatment of multi-level cervical spondylotic myelopathy (MCSM). Methods: Data of 121 patients meeting to inclusion criteria from October 2011 to February 2016 were retrospectively analyzed. All the patients were treated with ADF (ADF group, n=57) or LAMP (LAMP group, n=64) for MCSM. There were 39 males and 18 females in ADF group, aged from 35 to 77 years, with an average age of 58.8±10.1 years. And there were 64 cases in LAMP group, including 48 males and 16 females, aged from 28 to 82 years, with an average of 60.6±12.2 years. The operation time and blood loss were recorded. The clinical efficacy was evaluated by Japanese Orthopaedic Association Scores (JOA), improvement rate and visual analogue scale (VAS) before operation, 1, 3, 6, 12 and 24 months after operation and at the latest follow-up. At the same time, sagittal alignment of the C₂-C₇ lordotic angle and range of motion (ROM) in flexion and extension on plain X-rays was measured. Residual anterior compression to the spinal cord (ACS) in LAMP group on MRI was investigated. The incidence of complications such as axial symptoms and C₅ nerve root paralysis were recorded. Results: The average follow-up period was 25.6±3.8 months in ADF group and 27.3±4.1 months in LAMP group. Demographics were similar between the two groups. The mean JOA scores in ADF group increased from preoperative 8.25±2.33 to 14.62±3.15 at the latest follow-up, with an average recovery rate of 72.81%±11.32%. The mean JOA scores in LAMP group increased from preoperative 8.84±3.65 to 12.97±4.32 at the latest follow-up, with an average recovery rate of 66.54%±14.75%. The difference between two groups was statistically significant. Both of the VAS scores in the two groups decreased significantly at 1 month after the surgery, but the difference between the ADF group (1.92±0.75) and the LAMP group (2.78±0.68) was statistically significant (t=2.364, P=0.021). There was no significant difference in VAS score between the two groups at 3 months after operation. Cervical lordosis of ADF group increased from 15.3°±7.6° to 19.2°±5.7°, while that of LAMP group decreased from 16.8°±8.3° to 13.6°±4.3°. There was significant difference in cervical curvature between the two groups at the latest follow-up. Both two groups exhibited decreased cervical ROM, 15.2°±3.6° and 18.1°±4.1°, respectively, and the difference between two groups was statistically significant (t=3.392, P=0.000) . At the latest follow-up, the incidence of complication was 35.1% in ADF group and 20.3% in LAMP group, and the difference between two groups has no statistically significant. The LAMP group was divided into two subgroups: (1) ACS(+)(n=11) comprising patients who had ACS after surgery, and (2) ACS(-) (n=53) comprising patients without ACS. At the latest follow-up, the average JOA score of patients with anterior residual compression of spinal cord was 10.85±5.46, while the average JOA score of patients without anterior residual compression of spinal cord was 14.18±4.52. The recovery rate differed significantly between the ACS(+) and ACS(-) groups, 40.52%±9.76% and 70.38%±10.52%, respectively. Also at the latest follow-up, the cervical curvature, ROM and ROM loss angle were 10.2°±7.3°, 15.6°±6.7° and 11.8°±8.3° in the group with anterior residual compression of spinal cord, respectively. The groups without anterior residual compression of spinal cord were 15.8°±6.5°, 20.4°±10.2° and 8.8°±6.8°, respectively. Conclusion Both ADF and LAMP groups provided good outcomes at 2-year time-point whereas ADF could achieve more satisfactory outcomes and better sagittal alignment at the middle-term. ADF can remove the compression directly, maintain the curvature of cervical vertebra effectively and restore the nerve function well. The clinical outcomes after LAMP could be influenced by ACS, due to the reduction of cervical curvature and the decrease of cervical range of motion.