BACKGROUND Regarding the treatment of humeral shaft fractures, the choice of plating or intramedullary nailing remains controversial. Previous randomized controlled trials and meta-analyses failed to draw a unanimous conclusion. To guide clinical decision making, we conducted an updated meta-analysis on the optimal treatment of humeral shaft fractures. METHODS We identified eligible studies published from 1969 to July 2011 using the Cochrane Library; Cochrane Bone, Joint and Muscle Trauma Group; MEDLINE; Embase; OVID; and Google Scholar and manually searched the references of relevant studies. Randomized controlled trials that compared nailing and plating in the treatment of humeral shaft fractures were included. After the methodologic assessment, available data were extracted and statistically reviewed. The primary outcomes were nonunion, delayed union, postoperative infection, reoperation, and radial nerve palsy. The secondary outcomes were restriction of shoulder motion, shoulder impingement, iatrogenic fracture comminution, and implant failure. RESULTS We included 10 studies comparing plating and nailing in patients with humeral shaft fractures, comprising 439 participants. Plating reduced the risk of shoulder impingement and shoulder restriction in comparison with nailing. Regarding reoperation risk, a secondary sensitivity analysis showed the finding favoring plating over nailing remained unstable. Otherwise, no significant differences were found in postoperative infection, nonunion, delayed union, radial nerve palsy, iatrogenic fracture comminution, and implant failure between groups. CONCLUSIONS On the basis of current evidence, both plating and nailing can achieve a similar treatment effect on humeral shaft fractures, but plating may reduce the occurrence of shoulder problems. Randomized controlled trials with larger sample sizes using appropriate blinding methods are needed to confirm these findings. METHODS Level II, Meta-analysis of prospective comparative trials.