15 studies (839 patients) were included in this meta-analysis comparing plate fixation to intramedullary nailing for the treatment of humeral shaft fractures. Outcomes of interest included the American Shoulder and Elbow Surgeons (ASES) score, operative time, blood loss, and the incidence of non-union, nerve injury, post-operative infection, re-operation delayed union and shoulder and elbow joint restriction. A sub-group analyses was performed for each type of plate fixation. Pooled results found significantly favourable blood loss and incidence of post-operative infection with intramedullary nailing compared to plate fixation. The subgroup analyses revealed varying results: minimally-invasive plate osteosynthesis significantly outperformed intramedullary nailing in the incidence of non-union, intramedullary nailing significantly outperformed open reduction plate fixation in the incidence of post-operative infection, and open reduction plate fixation significantly outperformed intramedullary nailing in the incidence of shoulder and elbow joint restriction.