Study Design:This was a retrospective study.Objective:The objective of this study was to analyze risk factors of heterotopic ossification (HO) after cervical disk replacement (CDR) and evaluate the effect of footprint mismatch on HO.Summary of Background Data:Incidence of HO after CDR is high, but the exact related factors have not been fully elucidated.Materials and Methods:Radiographic data of patients who had undergone CDR with Prestige LP or Discover prosthesis in Tongji Hospital from July 2012 to December 2015 were reviewed. HO was graded according to McAfee classification and classified according to Jin morphologic classification. Footprint matching degree was evaluated using 3-dimensional computed tomographic images. Cervical sagittal alignment, functional spinal unit height, and range of motion were measured on radiographs. Preexisting degeneration was scored using Walraevens scoring system. Postulated risk factors including general factors, cervical sagittal alignment, functional spinal unit height, range of motion, postoperative biomechanical changes, preexisting degeneration, number of surgical levels, prosthesis type, use of nonsteroid anti-inflammatory drugs, and footprint matching degree were analyzed by first univariate tests, and then multivariate logistic regression was done to examine the relation with HO occurrence. Effect of footprint mismatch on type 1 HO of morphologic classification was evaluated.Results:Data of 46 patients were collected; 43 were finally evaluated with a total 57 prostheses implanted, with a mean follow-up duration of 41.1612.49 months. No significant differences in basic characteristics existed between 2 prosthesis groups, except follow-up time. Incidence of HO was 66.7%. Mean footprint matching degree in sagittal plane was 0.877 +/- 0.068 and in coronal plane was 0.852 +/- 0.092. Mean overall footprint matching degree was 0.699 +/- 0.102 (range: 0.388-0.993). Prosthesis type and footprint matching degree were significantly related with HO among all postulated risk factors in both univariate and multivariate analyses (P<0.05); the latter had larger Exp(B). Type 1 HO occurrence significantly related with footprint mismatch.Conclusions:Incidence of HO after CDR was high, and serious footprint mismatch existed. HO occurrence was significantly related with prosthesis type and footprint matching degree; the latter played a more important role.