: Anterior cervical discectomy and fusion (ACDF) is a common procedure for treating cervical spondylotic myelopathy. Limited research exists on the predictors of subsidence following ACDF. Subsidence can compromise surgical outcomes, alter alignment, and predispose patients to further complications, making it essential to prevent and understand it. This study aims to identify key risk factors for clinically significant subsidence and evaluate its impact on cervical alignment parameters in a large, diverse patient population. We conducted a retrospective review of patients who underwent ACDF between 2013 and 2022 at a single institution. Subsidence was calculated as the mean change in anterior and posterior disc height, with clinically significant subsidence being defined as three millimeters or more. Univariate analysis was followed by regression modeling to identify subsidence predictors and analyze patterns. Subgroup analyses stratified patients by implant type, number of levels fused, and cage material. : A total of 96 patients with 141 levels of ACDF met the inclusion criteria. Patients with significant subsidence were younger on average (52.44 vs. 55.94 years; = 0.074). Those with less postoperative lordosis were more likely to experience significant subsidence (79.5% vs. 90.2%; = 0.088). Patients with significant subsidence were more likely to have standalone implants (38.5% vs. 16.7%; < 0.01), taller cages (6.62 mm vs. 6.18 mm; < 0.05), and greater loss of segmental lordosis (7.33 degrees vs. 3.31 degrees; < 0.01). Multivariate analysis confirmed that standalone implants were a significant independent predictor of subsidence (OR 2.679; < 0.05), and greater subsidence was positively associated with loss of segmental lordosis (OR 1.089; < 0.01). Subgroup analysis revealed that multi-level procedures had a higher incidence of subsidence (35.7% vs. 28.1%; = 0.156), and PEEK cages demonstrated similar subsidence rates compared to titanium constructs (28.1% vs. 29.4%; = 0.897). : Standalone implants are the strongest independent predictor of significant subsidence, and those that experience subsidence also show greater loss of segmental lordosis, although not overall lordosis. These findings have implications for surgical planning, particularly in patients with borderline bone quality or requiring multi-level fusions. The results support the use of plated constructs in high-risk patients and emphasize the importance of individualized surgical planning based on patient-specific factors. Further research is needed to explore these findings and determine how they can be applied to improve ACDF outcomes.