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In vitro biomechanical analysis after cervical disc replacement (CDR) with a novel artificial disc prosthesis (mobile core) was conducted and compared with the intact model, simulated fusion, and CDR with a fixed-core prosthesis. The purpose of this experimental study was to analyze the biomechanical changes after CDR with a novel prosthesis and the differences between fixed- and mobile-core prostheses.Six human cadaveric C2–C7 specimens were biomechanically tested sequentially in 4 different spinal models: intact specimens, simulated fusion, CDR with a fixed-core prosthesis (Discover, DePuy), and CDR with a mobile-core prosthesis (Pretic-I, Trauson). Moments up to 2 Nm with a 75 N follower load were applied in flexion–extension, left and right lateral bending, and left and right axial rotation. The total range of motion (ROM), segmental ROM, and adjacent intradiscal pressure (IDP) were calculated and analyzed in 4 different spinal models, as well as the differences between 2 disc prostheses.Compared with the intact specimens, the total ROM, segmental ROM, and IDP at the adjacent segments showed no significant difference after arthroplasty. Moreover, CDR with a mobile-core prosthesis presented a little higher values of target segment (C5/6) and total ROM than CDR with a fixed-core prosthesis (P > .05). Besides, the difference in IDP at C4/5 after CDR with 2 prostheses was without statistical significance in all the directions of motion. However, the IDP at C6/7 after CDR with a mobile-core prosthesis was lower than CDR with a fixed-core prosthesis in flexion, extension, and lateral bending, with significant difference (P < .05), but not under axial rotation.CDR with a novel prosthesis was effective to maintain the ROM at the target segment and did not affect the ROM and IDP at the adjacent segments. Moreover, CDR with a mobile-core prosthesis presented a little higher values of target segment and total ROM, but lower IDP at the inferior adjacent segment than CDR with a fixed-core prosthesis.