Anterior cervical plate (ACP) failure is rarely addressed in the literature. In this retrospective, observational, longitudinal, cohort study, the objectives were to (1) identify incidences of in vivo biomechanical failure in commercially available, US Food and Drug Administration-approved ACP systems, (2) describe modes of failure, (3) suggest structural explanations for system failure, and (4) discuss complications and treatment of patients with failed ACP systems. Investigators retrospectively identified patients who underwent anterior cervical procedures followed by use of ACP as a fusion adjunct and showed evidence of ACP failure on plain radiographs. Components of the ACP system that led to failure were identified and examined. A total of 240 patients received ACP supplementation of anterior cervical fusion constructs during the 9.5-y study period. Evidence of ACP failure was noted in 7 patients (3.3%), and an eighth patient was referred for evaluation after ACP failure. Screw-plate interface failure occurred in all 8 cases. The biomechanical method by which the bone screw head was secured into the vertebral body, or against the ACP, the use of hybrid systems, the surgical technique selected, and host factors were used to determine the rate of failure. Concern for esophageal or other tissue injury often necessitated ACP removal. Screw-plate interface failure, which was found to be the most common mode of biomechanical ACP failure, may occur in hybrid constructs and in systems that do not create a rigid interface between the screw head and the ACP. Surgical technique and patient host factors may also influence the rate of biomechanical construct failure.