Background:Adjacent segment disease (ASD) following anterior cervical discectomy and fusion with plating (ACDF-P) may yield a poor prognosis or reoperation. This review aimed to summarize risk factors for radiographic ASD (RASD) and clinical ASD (CASD) after ACDF-P.Methods:Six electronic databases were searched from inception to October 30, 2021. Four reviewers independently screened titles, abstracts, and full-text articles to identify relevant studies. Methodological quality of the included studies was evaluated. Meta-analyses for risk factors were conducted, if possible.Results:Sixteen cohort and 3 case-control studies (3,563 participants) were included. These studies showed low (n = 2), moderate (n = 9), and high (n = 8) risk of bias. One risk factor for RASD was pooled for 2 meta-analyses based on the follow-up period. Four different risk factors for CASD at ≥4 years were pooled for meta-analyses. Limited evidence showed that multi-level fusion, greater asymmetry in total or functional cross-sectional area of the cervical paraspinal muscle, and preoperative degeneration in a greater number of segments were associated with a higher RASD incidence <4 years after ACDF-P. In contrast, no significant risk factors were identified for CASD <4 years after ACDF-P. At ≥4 years after ACDF-P, limited evidence supported that both cephalad and caudal plate-to-disc distances of <5 mm were associated with a higher RASD incidence, and very limited evidence supported that developmental canal stenosis, preoperative RASD, unfused C5-C6 or C6-C7 adjacent segments, use of autogenous bone graft, and spondylosis-related ACDF-P were associated with a higher CASD incidence.Conclusions:Although several risk factors for RASD and CASD development after ACDF-P were identified, the supporting evidence was very limited to limited. Future prospective studies should extend the existing knowledge by more robustly identifying risk factors for RASD and CASD after ACDF-P to inform clinical practice.Level of Evidence:Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.