Purpose The hypothesis for this study was that the simulated wear behavior of a hydroxyapatite coated, selfmating PEEK cervical disc arthroplasty device would be dependent on the simulated testing environment. Methods Five groups of devices were evaluated under suggested ASTM and ISO load and motion profiles. The groups utilized different testing frequencies and protein content of simulator fluid, in addition to assessing the potential for third body wear. The average wear rates were determined using linear regression analysis with a generalized estimating equation. Significant differences between groups were determined using the Wald's test. Results The simulated wear behavior was shown to be highly dependent on the testing environment, where protein content more than decreasing the cyclic loading frequency resulted in increased wear, but was not dependent on the suggested load and motion profiles. It was demonstrated that a self-mating PEEK cervical disc arthroplasty device has wear rates that are similar to existing material combinations for cervical disc arthroplasty. Conclusions This study showed that at a time when data from retrieval analyses is deficient, it is important to test the wear resistance of cervical disc arthroplasty devices under various conditions. Long-term clinical results and ongoing implant retrievals are required for validation between clinical performance and simulator inputs.