Compare the results of internal fixation of shaft of humerus fractures using dynamic compression plating (DCP) or antegrade interlocking intramedullary nail (IMN). Fifty patients with diaphyseal fracture of the shaft of the humerus and fulfilling the inclusion criterion were randomly assigned to one of the two groups. Twenty-five patients were managed with closed antegrade interlocking intramedullary nail, and 25 underwent open reduction and internal fixation using dynamic compression plating. The mean age of patients with IMN fixation was 37.28 years (SD 12.26) and 37.72 years (SD 12.70) for those who underwent plating. Road traffic accident was the most common mode of injury in both groups. There was a statistically significant difference between the two groups with respect to duration of hospital stay, operative time and blood loss. There was no significant difference between the two groups in terms of union or complications. The functional assessment at the end of 1 year between the two groups did not show any significant difference in outcome. Antegrade interlocking IMN and DCP fixation are comparable when managing diaphyseal shaft of humerus fractures with respect to union rates and complications. Although shoulder related complications are more in the IMN group, however, it is associated with shorter hospital stay, lesser operative time and less blood loss. This makes interlocking IMN an effective option in managing these fractures.