OBJECTIVE: Cervical disc replacement (CDR) is an effective long-term treatment for both cervical radiculopathy and myelopathy. However, there may be unique differences in the early postoperative clinical improvement for patients with and without myelopathy. In addition, previous studies using CDR to treat cervical myelopathy were underpowered to determine risk factors for relatively postoperative medical complications. METHODS: Two different cohorts were studied. A local cohort of patients undergoing CDR by a single surgeon was utilized to study the early postoperative course of clinical improvement. In addition, a national cohort of patients undergoing CDR in the 2015 and 2016 National Surgical Quality Improvement Program database was utilized to study differences in postoperative medical complications after CDR. Patients with a preoperative diagnosis of cervical myelopathy were identified in both cohorts, and perioperative outcomes and complications were compared to patients without myelopathy. RESULTS: A total of 43 patients undergoing CDR were included in the institutional cohort, of those 16 patients (37% of cohort) had a preoperative diagnosis of cervical myelopathy. A total of 3,023 patients undergoing CDR were included in the national cohort, of those 411 (13% of cohort) had a preoperative diagnosis of cervical myelopathy. In the institutional cohort, the nonmyelopathy group had a lower initial Neck Disability Index (NDI) and saw a faster improvement in NDI by 2 weeks postoperative. However, at 24 weeks there was no significant difference between groups in terms of NDI. Interestingly, only the nonmyelopathy cohort had a significant improvement in modified Japanese Orthopaedic Association score by 6 weeks (p<0.05). In the national cohort, myelopathy was associated with longer operative time and length of stay (p<0.05). However, there was no significant difference in perioperative complications (p>0.05) between myelopathy and nonmyelopathy patients. CONCLUSION: Significant improvements in NDI, visual analogue scale (VAS)-arm pain, and VAS-neck pain are seen in both myelopathy and nonmyelopathy populations undergoing CDR by 6 weeks postoperatively. However, nonmyelopathy populations improve faster by 2 weeks postoperatively. In the national cohort analysis, medical complications were similarly low in both myelopathy and nonmyelopathy groups.