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STUDY DESIGN A retrospective study with prospectively-collected data. OBJECTIVE To determine how type, location, and size of endplate lesions on magnetic resonance imaging (MRI) may be associated with symptoms and clinical outcomes after anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA Structural endplate abnormalities are important, yet understudied, phenomena in the cervical spine. ACDF is a common surgical treatment for degenerative disc disease; however, adjacent segment degeneration/disease (ASD) may develop. METHODS Assessed the imaging, symptoms and clinical outcomes of 861 patients who underwent ACDF at a single center. MRI and plain radiographs of the cervical spine were evaluated. Endplate abnormalities on MRI were identified and stratified by type (atypical, typical), location, relation to operative levels, presence at the adjacent level, and size. These strata were assessed for association with presenting symptoms, patient-reported, and postoperative outcomes. RESULTS Of 861 patients (mean follow-up: 17.4 months), 57.3% had evidence of endplate abnormalities, 39.0% had typical abnormalities, while 18.2% had atypical abnormalities. Patients with any endplate abnormality had greater odds of myelopathy irrespective of location or size, while sensory deficits were associated with atypical lesions (P = 0.016). Typical and atypical abnormalities demonstrated differences in patient-reported outcomes based on location relative to the fused segment. Typical variants were not associated with adverse surgical outcomes, while atypical lesions were associated with ASD (irrespective of size/location; P = 0.004) and reoperations, when a large abnormality was present at the proximal adjacent level (P = 0.025). CONCLUSION This is the first study to examine endplate abnormalities on MRI of the cervical spine, demonstrating distinct risk profiles for symptoms, patient-reported, and surgical outcomes after ACDF. Patients with typical lesions reported worsening postoperative pain/disability, while those with atypical abnormalities experienced greater rates of ASD and reoperation. This highlights the relevance of a degenerative spine phenotypic assessment, and suggests endplate abnormalities may prognosticate clinical outcomes after surgery. LEVEL OF EVIDENCE 3.