BACKGROUND CONTEXT: While cervical disc replacement (CDR) has been emerging as a reliable and efficacious treatment option for degenerative cervical spine pathology, not all patients undergoing CDR will achieve minimal clinically important difference (MCID) in patient-reported outcome measures (PROMs) postoperatively-risk factors for failure to achieve MCID in PROMs following CDR have not been established. PURPOSE: To identify risk factors for failure to achieve MCID in Neck Disability Index (NDI, Visual Analog Scale (VAS) neck and arm following primary 1- or 2-level CDRs in the early and late postoperative periods. STUDY DESIGN: Retrospective review of prospectively collected data. PATIENT SAMPLE: Patients who had undergone primary 1- or 2-level CDR for the treatment of degenerative cervical pathology at a single institution with a minimum follow-up of 6 weeks between 2017 and 2022. OUTCOME MEASURES: Patient-reported outcomes: Neck disability index (NDI), Visual analog scale (VAS) neck and arm, MCID. METHODS: Minimal clinically important difference achievement rates for NDI, VAS-Neck, and VAS-Arm within early (within 3 months) and late (6 months to 2 years) postoperative periods were assessed based on previously established thresholds. Multivariate logistic regressions were performed for each PROM and evaluation period, with failure to achieve MCID assigned as the outcome variable, to establish models to identify risk factors for failure to achieve MCID and predictors for achievement of MCID. Predictor variables included in the analyses featured demographics, comorbidities, diagnoses/symptoms, and perioperative characteristics. RESULTS: A total of 154 patients met the inclusion criteria. The majority of patients achieved MCID for NDI, VAS-Neck, and VAS-Arm for both early and late postoperative periods-79% achieved MCID for at least one of the PROMs in the early postoperative period, while 80% achieved MCID for at least one of the PROMs in the late postoperative period. Predominant neck pain was identified as a risk factor for failure to achieve MCID for NDI in the early (OR: 3.13 [1.10-8.87], p-value: .032) and late (OR: 5.01 [1.31-19.12], p-value: .018) postoperative periods, and VAS-Arm for the late postoperative period (OR: 36.63 [3.78-354.56], p-value: .002). Myelopathy was identified as a risk factor for failure to achieve MCID for VAS-Neck in the early postoperative period (OR: 3.40 [1.08-10.66], p-value: .036). Anxiety was identified as a risk factor for failure to achieve MCID for VAS-Neck in the late postoperative period (OR: 6.51 [1.91-22.18], p-value: .003). CDR at levels C5C7 was identified as a risk factor for failure to achieve MCID in NDI for the late postoperative period (OR: 9.74 [1.43-66.34], p-value: .020). CONCLUSIONS: Our study identified several risk factors for failure to achieve MCID in common PROMs following CDR including predominant neck pain, myelopathy, anxiety, and CDR at levels C5-C7. These findings may help inform the approach to counseling patients on outcomes of CDR as the evidence suggests that those with the risk factors above may not improve as reliably after CDR.