We randomised prospectively 44 patients with fractures of the shaft of the humerus to open reduction and internal fixation by either an intramedullary nail (IMN) or a dynamic compression plate (DCP). Patients were followed up for a minimum of six months. There were no significant differences in the function of the shoulder and elbow, as determined by the American Shoulder and Elbow Surgeons' score, the visual analogue pain score, range of movement, or the time taken to return to normal activity. There was a single case of shoulder impingement in the DCP group and six in the IMN group. Of these six, five occurred after antegrade insertion of an IMN. In the DCP group three patients developed complications, compared with 13 in the IMN group. We had to perform secondary surgery on seven patients in the IMN group, but on only one in the DCP group (p = 0.016). Our findings suggest that open reduction and internal fixation with a DCP remains the best treatment for unstable fractures of the shaft of the humerus. Fixation by IMN may be indicated for specific situations, but is technically more demanding and has a higher rate of complications.