Background: The goal of this study was to compare the effectiveness of a rotator cuff-sparing postero-inferior (PI) approach with subdeltoidal access to the traditional subscapularis-takedown deltopectoral approach, in terms of implant sizing and positioning in anatomical total shoulder arthroplasty (aTSA). Methods: This study involved 18 human cadaveric shoulders with intact rotator cuffs and no evidence of head deforming osteoarthritis. An Eclipse stemless aTSA (Arthrex, Naples, FL, USA) was implanted in nine randomly selected specimens using a standard subscapularis-tenotomy deltopectoral approach, and in the other nine specimens using the cuff-sparing PI approach. Pre- and postoperative antero-posterior (AP) and axillary fluoroscopic radiographs were analyzed by two independent, blinded raters for the following parameters: (1) anatomic and prosthetic neck-shaft angle (NSA); (2) the shift between the anatomic and prosthetic center of rotation (COR); (3) anatomical size matching of the prosthetic humeral head; (4) the calculated Anatomic Reconstruction Score (ARS); (5) glenoid positioning; as well as (6) glenoid inclination and version. Results: While the COR was slightly but significantly positioned (p = 0.031) to be more medial in the PI approach group (3.7 ± 3.4%, range: −2.3% to 8.7%) than in the deltopectoral approach group (−0.2 ± 3.6%, range: −6.9% to 4.1%), on average, none of the remaining measured radiographic parameters significantly differed between both groups (PI approach group vs. deltopectoral group: NSA 130° vs. 127°, p = 0.57; COR supero-inferior, 2.6% vs. 1.0%, p = 0.35; COR antero-posterior, 0.9% vs. 1.7%, p = 0.57; head size supero-inferior, 97.3% vs. 98.5%, p = 0.15; head size antero-posterior, 101.1% vs. 100.6%, p = 0.54; ARS, 8.4 vs. 9.3, p = 0.13; glenoid positioning supero-inferior, 49.1% vs. 51.1%, p = 0.33; glenoid positioning antero-posterior, 49.3% vs. 50.4%, p = 0.23; glenoid inclination, 86° vs. 88°, p = 0.27; and glenoid retroversion, 91° vs. 89°, p = 0.27). Conclusions: A PI approach allows for sufficient exposure and orientation to perform rotator-cuff sparing aTSA with acceptable implant sizing and positioning in cadaveric specimens.