92 patients with acute mid-shaft humeral fractures, scheduled for ORIF with a locked intramedullary nailing within 2 weeks of injury, were randomized to be fixed by antegrade or retrograde technique. Patients were followed-up for a minimum of 14 months and assessed for outcomes of fracture healing, time to healing, functional recovery, time to functional recovery, and complications experienced. Antegrade and retrograde nailing were equally effective in terms of healing rate and eventual functional recovery. Antegrade nailing resulted in a longer recovery period for shoulder functional improvement; conversely, retrograde nailing resulted in a longer period for elbow functional recovery.