Anterior cervical discectomy and fusion (ACDF) immobilizes surgical segments and can lead to the development of adjacent segment degeneration and adjacent segment disease. Thus, cervical total disc replacement (CTDR) has been developed with the aim to preserve the biomechanics of spine. However, heterotopic ossification (HO), a complication following CTDR, can reduce the segmental range of motion (ROM) and defects the motion-preservation benefit of CTDR. The pathological process of HO in CTDR remains unknown. HO has been suggested to be a self-defense mechanism in response to the non-physiological biomechanics of the cervical spine following CTDR. The current literature review is concerned with the association between the biomechanical factors and HO formation and the clinical significance of HO in CTDR. Endplate coverage, disc height, segmental angle, and center of rotation may be associated with the development of HO. The longer the follow-up, the higher the rate of ROM-limiting HO. Regardless of the loss of motion-preservation benefit of CTDR in patients with HO, CTDR confers patients with a motion-preservation period before the development of ROM-limiting HO. This may delay the development of adjacent segment degeneration compared with ACDF. Future clinical studies should explore the association between HO and changes in biomechanical factors of the cervical spine.