Background: Glenoid component failures still represent the most common complication in total shoulder arthroplasty. These failures depend on several factors, including ultra-high molecular weight polyethylene (UHMWPE) wear. One reason for UHMWPE wear in total shoulder arthroplasty may be the current use of a spherical prosthetic humeral head against a radially mismatched UHMWPE glenoid component, which leads to reduced glenohumeral translations, glenoid edge loading and high translational forces during shoulder motions. The aim of this study was to assess the in vitro wear of an anatomic total shoulder prosthesis with non-spherical non-conforming bearings with inverted conventional materials. Methods: The wear of a vitamin E-blended UHMWPE non-spherical humeral head articulating against a non-conforming titanium-niobium nitride (TiNbN)-coated metallic glenoid was tested using a joint simulator. The wear test was performed by applying a constant load of 756 N with angular motions and translations. Results: After 2.5 million cycles, the mean wear rate of the humeral head was 0.28 AE standard deviation (SD) 0.45 mg/million cycles. Conclusion: The low wear rate of the vitamin E UHMWPE humeral head supports the use of non-spherical nonconforming bearings with inverted conventional materials in anatomic total shoulder arthroplasty. Keywords ultra-high molecular weight polyethylene wear, total shoulder arthroplasty, non-spherical humeral head, inverted bearing materials, non-conforming bearings Date