Background:A fracture of the humerus shaft is commonly encountered by orthopedic surgeons and the successful treatment of a humeral shaft fracture demands a knowledge of anatomy, surgical indications, techniques and implants, patient functions and expectations. The aim of the current study was to compare the outcome of interlocking intramedullary nailing versus plating of diaphyseal humeral shaft fracture in adults Patients and Methods: This prospective clinical trial was carried in Orthopedic Department, Zagazig Universityin Egypt Hospitals and Alwahda Hospital in Libya, on 36 cases with Humeral shaft fractures Group 1: included 18 patients managed by Intramedullary Nailing, Group 2: included 18 patients managed by plating during the period from March 2020 to December 2020.Patients were followed post operatively for union, and clinical assessment was done using The American Shoulder and Elbow Surgeons scale. Results:Radial nerve injury was significantly higher in plate group and delayed union and nonunion was higher in nail with no significant.Excellent represent 72.2% in nail group and 66.7% in plate group, good represent 11.1% of both groups and fair founded 16.7% in plate group and 5.6% in nail group 2 cases were poor in Nail and 1 case was poor in plate Nail group was significantly associated with satisfaction. Conclusion: The intramedullary nail fixation for humerus is treatment of choice in osteoporotic bone, less rate of infection less blood loss, however it associated with higher incidence of shoulder discomfort, and more malunion and non unuon rate