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Background: In vitro data demonstrate the potential benefits of the pyrocarbon as a bearing material against cartilage or bone. And pyrocarbon-free interposition arthroplasty has been used with positive outcomes for over 10 years for hand and wrist joint replacements. This study reports the midterm results of a Pyrocarbon Interposition Shoulder Arthroplasty (PISA) in primary and secondary glenohumeral osteoarthritis and in avascular osteonecrosis. Methods: This prospective noncontrolled, multicenter study included 67 consecutive patients who underwent PISA in France and Sweden. Results: A cohort of 48 patients, aged 50 ± 12 years, was available for clinical assessment at a mean follow-up of 67.6 ± 9.3 months. A favorable change was reported with a mean absolute Constant score improvement of 32 ± 20 points. The highest Constant score improvement was observed in patients with avascular osteonecrosis (42 ± 18 points; P ≤ .0001). Between the earliest and the latest follow-up, radiographic analyses revealed only 2 major glenoid erosions and 4 tuberosity thinnings and thus that 86.4% of 44 shoulders remained stable with no or minor radiologic evolutions. The survival rate was 84 % at 65 months of follow-up considering all causes of revision. Conclusion: The radiographic findings seem to confirm the interest of pyrocarbon in preserving bony surfaces. But the risk of tuberosity thinning suggests considering the use of PISA with caution in most degenerative glenohumeral joint pathologies, although the midterm outcomes highlight PISA as a suitable solution for patients presenting with posttraumatic osteonecrosis without malunion of the tuberosities and with an intact rotator cuff.