The goal of this study was to define safe zones to prevent radial nerve injury in an extended deltopectoral approach. Relative distances of the upper margin (UMRN) and lower margin (LMRN) of the radial nerve to the proximal and distal borders of the pectoralis major and deltoid insertions were measured in 20 cadaveric arms. Four proximal humeral zones were identified (zone I, proximal border of the pectoralis major tendon to the proximal border of the deltoid tendon; zone II, proximal border of the deltoid tendon to the distal border of the pectoralis major tendon; zone III, distal border of the pectoralis major tendon to the distal border of the deltoid tendon; and zone IV, distal to the distal border of the deltoid tendon). On fluoroscopic measurement, mean distances between the UMRN and the proximal border of the pectoralis major tendon and the proximal border of the deltoid tendon were 71.6±2.1 mm and 26.2±2.5 mm, respectively. The incidence of the radial nerve in the spiral groove within each defined zone was as follows: zone I, 0%; zone II, 50%; zones III and IV, 100%. There was a significant association between anatomic zone and radial nerve entry into the spiral groove, χ2(3, N=88)=64.53, P<.001. The proximal border of the pectoralis major tendon to the proximal border of the deltoid tendon (zone I) is a safe location to avoid injury to the radial nerve. We recommend placing cerclage wires proximal to zone I from lateral to medial to avoid entrapment of the radial nerve. [Orthopedics. 2023;46(1):e31-e37.].