Background: Adjacent segment degeneration (ASD) is a concern in multi-level ACDF surgery. Hybrid surgery with C-ADR and ACDF are an alternative treatment to reduce the level of increased rigidity, but biomechanical differences between strategies using one C-ADR and two ACDFs have not been thoroughly investigated.Methods: To evaluate the placement-related effects of using one cervical artificial disc replacement (C-ADR) and two anterior cervical discectomy and fusion (ACDF) on tissue responses and implant behavior. A nonlinear finite element model from the C2 to the T1 vertebrae was developed. Ligament interconnection, follower loads, and weight compression were used to simulate cervical flexion. Within the C4-C7 segments, two placements of one C-ADR and two ACDFs were arranged: PAP (peek cage, artificial disc, and peek cage) and APP.Results: Both PAP and APP consistently induced kinematic and mechanical redistribution to adjacent segments. The C-ADR served as a buffer of the compensated motion and stress from the ACDF segments. The motion and stress of the cranial C2-C3 and C3-C4 segments were greater for the PAP than the APP constructs. However, the caudal C7-T1 segment of the APP construct was more flexed and stressed. Serially stacked cages of the APP placement increased bone-cage stresses, potentially inducing subsidence and loosening. The sandwiched C-ADR of the PAP construct accommodated the compensated motion and stress from the adjacent ACDFs more than the APP construct.Conclusions: The PAP and APP placements cause more severe ASD progression at the cranial and caudal segments, respectively. The PAP placement is preferred for concerns regarding ACDF and postoperative degeneration of caudal segments. The APP placement is recommended when C-ADR failure and ASD progression are considered.