Study DesignSystematic review and meta-analysis.ObjectiveThis meta-analysis aimed to compare hybrid surgery (HS) and two-level anterior cervical discectomy and fusion (ACDF) in the treatment of consecutive two-level cervical degenerative disc disease (CDDD).MethodsComprehensive searches were conducted in PubMed, Embase, and Web of Science. Extracted data from the selected studies included operative time, intra-operative blood loss, C2-C7 range of motion (C2-C7 ROM), superior adjacent segment range of motion (SAS ROM), inferior adjacent segment range of motion (IAS ROM), complication incidence, neck disability index (NDI) score, Japanese Orthopaedic Association (JOA) score, and visual analogue scale (VAS) score. Meta-analysis was conducted using RevMan 5.3.ResultsA total of 626 patients from 11 studies who underwent either HS or two-level ACDF for CDDD were analyzed. Compared to ACDF in the non-ROI-C cage group, HS better preserved post-operative and final follow-up C2-C7 ROM (post-operation: MD 10.08, 95% CI 6.58 to 13.58, 0.01; final follow-up: MD 7.62, 95% CI 5.83 to 9.42, 0.01). HS significantly reduced post-operative and final follow-up SAS ROM and IAS ROM at the final follow-up. Additionally, HS resulted in less intraoperative blood loss than ACDF when blood loss reached 90 mL or more. Analysis of functional scores (NDI, JOA, and VAS), operative time, and complication rates showed no significant differences between HS and ACDF.ConclusionHS achieved better radiographic outcomes compared to two-level ACDF, with comparable clinical outcomes, reduced intraoperative blood loss, and a similar complication rate. However, further high-quality randomized controlled trials are needed.