Objectives: To compare the functional outcome of dynamic compression plating with intramedullary interlocking nailing in closed fracture of the humeral shaft in adults. Study Design: Prospective comparative study. Setting: Department of orthopedics, Civil hospital, Karachi. Period: From 8th February to 7th August 2017. Material & Methods: A total of 82 patients with post-traumatic closed fracture shaft of the humerus were included. Patients were randomly allocated into two groups. Group I was offered Intramedullary Interlocking nail (ILN) and Group II was offered a dynamic compression plate (DCP). The functional outcome was measured by the “Disabilities of Arm, Shoulder and Hand” (DASH) score. Results: The average age of the patients was 32.87±6.65 years. The acceptable outcome was significantly high in DCP group as compared to the ILN group (87.8% vs. 61%; p = 0.005). Conclusion: We conclude that dynamic compression plating is functionally a better technique than interlocking nailing for closed fracture of shaft of the humerus in adults.