Background: Rotator cuff muscle degeneration is an important parameter to consider when planning shoulder arthroplasty. Hypothesis: We hypothesized that rotator cuff muscle degeneration is correlated with scapulohumeral subluxation in patients planned for anatomical total shoulder arthroplasty (TSA). Materials and methods: We developed a semi-automated quantitative CT method to measure rotator cuff muscle degeneration, and retrospectively analyzed 107 preoperative shoulder CT scans of patients with primary osteoarthritis. On a standardized sagittal-oblique CT slice perpendicular to the scapular axis, two observers measured the cross-sectional areas of residual rotator cuff muscle tissues, normalized by the estimated area of healthy muscles. Muscle degeneration was quantified in a semi-automated manner, and divided into atrophy and fatty infiltration. Scapulohumeral subluxation was determined in 3D as the distance between the humeral head center and the glenoid surface center, projected on the same CT slice, and normalized by the humeral head radius. We tested all potential correlations between muscle degeneration and scapulohumeral subluxation. Results: Muscle degeneration, primarily due to atrophy, predominated in the supraspinatus; it varied from 0.8% to 88.8%. Scapulohumeral subluxation varied from 2.5% to 72.9%, and was mainly in a posterior and postero-superior orientation. There was a significant but weak correlation between the amount of sublux- ation and both supraspinatus (R = 0.207, P = 0.032) and infraspinatus (R = 0.225, P = 0.020) degeneration. Inter- and intra-observer reproducibility of muscle degeneration measurements were both excellent (ICCs range = 0.955–0.987 and 0.971–0.988, respectively). Conclusion: This new semi-automated CT method allows to quantitatively and reproducibly measure rotator cuff muscle degeneration in shoulders with primary osteoarthritis. Muscle degeneration is weakly correlated with scapulohumeral subluxation in patients planned for anatomical TSA.