Fractures of humeral shaft are commonly seen in orthopaedic practice accounting for approximately 3% of all fractures. Treatment of these injuries continue to evolve as advances are made in both nonoperative and operative management. We performed a prospective study in the management of fractures of diaphysis of humerus by interlocking nail fixation and dynamic compression plating (DCP) was undertaken over a period of 3 years. Forty five patients with humerus fracture were treated with either interlocking nailing or plating. Rodriguez-Merchan et al criteria was used to compare results of both groups postoperatively. Fractures with unacceptable alignment was the most common indication for operative intervention (53%). While only 50% of the interlocking group had healed by 16 weeks, 75% of the plating group had united by this time. Overall results (Rodriguez-Merchan) show 65% excellent and good results in interlocking group and 93% similar results in the plating group. Postoperative radial nerve palsy was not seen in the interlocking group but was noted in 6.25% of the plating group. All of them recovered uneventfully with time. Plating is generally considered gold standard and to have predictable results in treatment of humerus shaft fractures. We have noted earlier union and better overall results in the plating group. Interlocking nailing is particularly preferable in communited, segmental and pathological fractures.