Background: The anatomy of the proximal part of the humerus is extremely variable. The extent to which existing prosthetic systems and operative technique allow replication of this variability has not been established.Methods: Four commonly used press-fit prosthetic systems for shoulder arthroplasty were compared with respect to their ability to match the superior-inferior and medial-lateral dimensions of the articular surface in twenty-one cadaveric humeri. The comparisons were accomplished with a computer optimization algorithm that searched a database of prosthetic geometry and selected the best match to the original anatomy. The algorithm assumed an osteotomy of the humeral head at an angle equivalent to the stem-head angle of the prosthesis, without violation of the greater tuberosity or the metaphyseal bone. The best match was defined as the prosthetic combination (stem and head) that least displaced the center of rotation and the articular surface, with both factors weighted equally.Results: None of the prosthetic systems that were evaluated allowed identical replication of the articular surface. Rather, they displaced the center of rotation a mean of 14.7 millimeters (range, 3.3 to 31.4 millimeters) from its original position. To reach this minimized displacement, the prosthetic combinations that were selected by the algorithm also resulted in a mean diminution of the arc of the articular surface (a smaller head size) of 26 degrees (range, 11 to 41 degrees). In every instance, the selected prosthesis imposed a superior and lateral shift of the center of rotation that in effect shifted a smaller prosthetic humeral head up the slope of the humeral osteotomy.Conclusions: Press-fit prosthetic systems for shoulder arthroplasty that are commonly used necessitate marked alterations of the original anatomy. To the extent that a shoulder arthroplasty is an attempt to reproduce the normal anatomy, these findings have profound implications for operative technique and future prosthetic design.Clinical Relevance: We believe that the superior position of the prosthetic head predicted by the present study plays a role in late complications of shoulder arthroplasty, such as rotator cuff tendinopathy, superior humeral migration, and loosening of the glenoid component.