Background: Humeral shaft fractures represent 3% of all fractures, a significant number of these fractures require operative intervention. Objective: To compare the results of plate osteosynthesis and interlocking nailing in the treatment of diaphyseal humeral fracture concerning rate healing, functional outcome, and complications. Patients and Methods: This study is a prospective comparative study that included 18 patients in the period from December 2018 to July 2019 with follow up 8 months were operated up on at the Orthopedic Surgery Department of Zagazig University Hospitals. All patients had closed fractures in both groups. The commonest mechanism of injury was road traffic accidents (RTA) in 7 patients were in group I, 4 patients in group II. Falling from height in 3 patients were in group I and 4 patients were in group II. 9 cases of them were fixed by plates (group 1) and the other 9 by IM nails (group 2). Results: The results obtained were excellent in 15 patients (83.3%) 6 patient fixed with a plate (66.6%) and 9 patient fixed with nail (100%), good in 2 patients (11.1%) fixed with plate and Fair in one patient (5.5%) fixed with a plate. The excellent and good results were considered satisfactory while fair and poor results were considered unsatisfactory. Conclusions: Plate fixation offered a higher likelihood of anatomic reduction of the fractures and predictable healing results, provided AO principles were followed. Although not quantifiable, it was our impression that antegrade nails were advantageous in comminuted AO Type C fractures.