Objectives The aim of this study was, firstly, to analyse the long-time fatigue behaviour of crowns constructed from a novel polyetherketoneketone (PEKK) polymer, using artificial prepared teeth. Secondly, to determine the effect of the material’s stiffness that used as an artificial prepared tooth on the fatigue life of the PEKK crowns in comparison to human prepared teeth. Methods Veneered crowns with a PEKK framework were constructed on three different prepared teeth: artificial polymethyl methacrylate (PMMA) teeth, artificial CoCr teeth and extracted human teeth. As far as applicable, the loading protocol was based on EN ISO 14801:2007 for fatigue testing of dental implants. After initial static fracture tests on three specimens from each group, the remaining crowns were loaded with different force levels until fracture or until 2 × 106 loading cycles were reached. The number of loading cycles until failure was recorded. Wöhler curves were created to display the fatigue limits. Results Static fracture limits as well as fatigue limits differed for all three core materials. The static fracture tests resulted in fracture limits of 1200 (± 293) N for the PMMA group, 1330 (± 219) N for the CoCr group and 899 (± 96) N for the human tooth group. Fatigue limits of 770 N, 840 N and 720 N were determined for the PMMA group, CoCr group and human tooth group, respectively. Conclusions The determined fatigue limit of above 720 N (depending on the core material) is sufficiently high and a good performance of this crown material is expected in the clinical loading life. The results showed that using artificial teeth instead of natural teeth for fatigue testing of crowns might result in an overestimation of the fatigue limits of the crown material. Clinical relevance PEKK-made crowns offer a stable and priceworthy treatment for patients, in particular those that suffer from metal allergy.