Objective To identify the anatomic advantages of pre-contouring long helical plate of proximal humerus internal locking system (PHILOS) aided by 3D-printing technique in minimally invasive plate oseoynthesis (MIPO) for metadiaphyseal fractures of the proximal humerus. Methods Firstly in a cadaveric study, 12 fresh frozen samples of upper extremity were divided into 2 equal groups: 6 in a Synbone group and 6 in a 3D-printing group. Long 10-hole PHILOS plates were pre-contoured helically according to Synbone humerus models in the Synbone group but according to 3D-printing humerus models in the 3D-printing group. All these helical plates were fixed onto the cadaveric humerus using MIPO technique respectively. The horizontal distances between the radial nerve and the lateral side of the plate were measured at the point where the radial nerve penetrates the muscular septum, at the 6th hole on the plate and at the distal end of the plate; the distance between the medial side of the distal plate and the upper arm neurovascular bundle was also measured. Finally, the full lengths of all these cadaveric humeri were measured. Secondly, on the basis of the anatomic study, 16 patients with metadiaphyseal fracture of the proximal humerus were treated at Department of Orthopedic Surgery, The Sixth People’s Hospital of Shanghai from February 2013 to March 2016, using the same MIPO technique and the same long 10-hole PHILOS plates pre-contoured helically on the 3D printing models which were mirrored on the humerus on the healthy side of the patients. They were 4 men and 12 women, aged from 59 to 87 years (mean, 71.0 years). By the AO/OTA classification, 10 cases were type B and 6 type C. The fracture line involved the proximal humerus in 7 cases. Postoperative complications were followed up. At the final follow-up, the shoulder function was assessed according to the Constant-Murley score and the elbow function according to the Mayo Elbow Performance Score (MEPS). Results By the anatomic measurement, the full length of cadaveric humerus averaged 30.17±1.93 cm in the Synbone group and 29.75±2.17cm in the 3D-printing group, showing no significant difference (P>0.05). The horizontal distances between the radial nerve and lateral side of the plate at the point where the radial nerve penetrates the muscular septum, at the 6th hole on the plate and at the distal end of the plate in the Synbone and 3D-printing groups were, respectively, 11.50±0.92 mm versus 17.87±1.88 mm, 6.90±1.78 mm versus 14.83±1.50 mm, and 5.14±1.14 mm versus 8.36±1.27 mm, all showing significant differences between the 2 groups (P 0.05). The clinical observation found no iatrogenic nerve injury. The 16 patients were followed up for an average of 25.3 months (range, from 24 to 38 months). All fractures got united uneventfully. At the final follow-up, their Constant-Murley scores averaged 77.6 points and their MEPS 96.5 points. Conclusion The risk of iatrogenic injury to the radial nerve can be lowered when 3D-print technique is applied for helical pre-contouring of long PHILOS plate in the MIPO for metadiaphyseal proximal humeral fractures, leading to satisfactory clinical results. Key words: Humeral fractures; Fracture fixation, internal; Anatomy; Clinical trial; 3D printing technology