The role of the subscapularis (Ssc) tendon does not yet have a well-defined role in RSA. The purpose of the present study was to evaluate if the repair of the Ssc in RSA improves overall clinical and radiographic results and if it has the same results using a medialized design humeral stem compared to a lateralized design. Eighty-four consecutive patients undergoing RSA were retrospectively analyzed. Nine patients were lost at FU. Two implants with similar glenosphere design and different stem design (medialized and lateralized) were used. The Ssc was repaired in case of good quality of the fibers and reducibility without tension intraoperatively. Patients were divided into four groups for data analysis depending on whether they had received a medialized or lateralized design and Ssc repair or not. Patients were reviewed at an average follow-up of 40.8 ± 13.1months. Clinical outcome measures included Active range of motion (ROM), strength, visual analog scale (VAS), Constant-Murley score (CMS), and the American Shoulder and Elbow Surgeons score (ASES). Radiographic evaluation at final follow-up was performed to assess scapular notching, stress shielding, and radiolucent lines. No statistically significant clinical differences (p > 0.05) emerged between Lat/Ssc+ and Lat/Ssc-. Conversely, the patients belonging to the Med/Ssc- group reported statistically worse (p < 0.05) results than the Med/Ssc + group in terms of VAS, ASES and CMS. Statistically worse (p < .05) results in the Med/Ssc- group than in the Med/Ssc + were found also in active ROM achieved in FE, ABD, ER1 and ER2, and in the strength obtained in FE, ABD and ER2. Scapular notching was reported in 3 shoulders (15.7%) in Lat/Ssc+ group and in 7 shoulders (50%) in Lat/Ssc- group, while it was reported in 4 shoulders (14.2%) in Med/Ssc + group and in 6 shoulders (42.8%) in Med/Ssc- group. Stress shielding was observed in 6 cases in Lat/Ssc+ group (31.6%), in 8 cases in Lat/Ssc- group (57.1%), in 3 cases (10.7%) in Med/Ssc + group and 4 cases in Med/Ssc- group (28.6%). Patients undergoing RSA show clinical improvements at mid-term follow-up with a low rate of complications, regardless of the use of a medialized or a lateralized humeral stem design. Ssc repair is associated with better functional outcomes in the cohort of medialized stem, while it did not yield significant differences in the cohort of lateralized stem. Level III; Retrospective Cohort Comparison; Treatment Study.