OBJECT Heterotopic ossification (HO) after cervical arthroplasty is not uncommon and may cause immobility of the disc. To prevent HO formation, study protocols of clinical trials for cervical arthroplasty undertaken by the US FDA included perioperative use of nonsteroidal antiinflammatory drugs (NSAIDs). However, there are few data supporting the use of NSAIDs to prevent HO after cervical arthroplasty. Therefore, this study aimed to evaluate the efficacy of NSAIDs in HO formation and clinical outcomes. METHODS Consecutive patients who underwent 1- or 2-level cervical arthroplasty with a minimum follow-up of 24 months were retrospectively reviewed. All patients were grouped into 1 of 2 groups, an NSAID group (those patients who had used NSAIDs postoperatively) and a non-NSAID group (those patients who had not used NSAIDs postoperatively). The formation of HO was detected and classified using CT in every patient. The incidence of HO formation, disc mobility, and clinical outcomes, including visual analog scale (VAS) scores of neck and arm pain, neck disability index (NDI) scores, and complications were compared between the two groups. Furthermore, a subgroup analysis of the patients in the NSAID group, comparing the selective cyclooxygenase (COX)-2 to nonselective COX-2 NSAID users, was also conducted for each of the above-mentioned parameters. RESULTS A total of 75 patients (mean age [± SD] 46.71 ± 9.94 years) with 107 operated levels were analyzed. The mean follow-up duration was 38.71 ± 9.55 months. There were no significant differences in age, sex, and levels of arthroplasty between the NSAID and non-NSAID groups. There was a nonsignificantly lower rate of HO formation in the NSAID group than the non-NSAID group (47.2% vs. 68.2%, respectively; p = 0.129). During follow-up, most of the arthroplasty levels remained mobile, with similar rates of immobile discs in the NSAID and non-NSAID groups (13.2% and 22.7%, respectively; p = 0.318). Furthermore, there was a nonsignificantly lower rate of HO formation in the selective COX-2 group than the nonselective COX-2 group (30.8% vs 52.5%, respectively; p = 0.213). The clinical outcomes, including VAS neck, VAS arm, and NDI scores at 24 months postoperatively, were all similar in the NSAID and non-NSAID groups, as well as the selective and nonselective COX-2 groups (all p > 0.05). CONCLUSIONS In this study there was a trend toward less HO formation and fewer immobile discs in patients who used postoperative NSAIDs after cervical arthroplasty than those who did not, but this trend did not reach statistical significance. Patients who used selective COX-2 NSAIDs had nonsignificantly less HO than those who used nonselective COX-2 NSAIDs. The clinical outcomes were not affected by the use of NSAIDs or the kinds of NSAIDs used (selective vs nonselective COX-2). However, the study was limited by the number of patients included, and the efficacy of NSAIDs in the prevention of HO after cervical arthroplasty may need further investigation to confirm these results.