There is a debate regarding the choice of operative intervention in humeral shaft fractures that require surgical intervention. The choices for operative interventions include intramedullary nailing (IMN) and dynamic compression plate (DCP). This meta-analysis was performed to compare fracture union, functional outcomes, and complication rates in patients treated with IMN or DCP for humeral shaft fractures and to develop GRADE (Grading of Recommendations, Assessment, Development, and Evaluation)-based recommendations for using the procedures to treat humeral shaft fractures. A systematic search of all the studies published through December 2012 was conducted using the Medline, Embase, Sciencedirect, OVID and Cochrane Central databases. The randomized controlled trials (RCTs) and quasi-RCTs that compared IMN with DCP in treating adult patients with humeral shaft fractures and provided data regarding the safety and clinical effects were identified. The demographic characteristics, adverse events and clinical outcomes were manually extracted from all of the selected studies. Ten studies that included a total of 448 patients met the inclusion criteria. The results of a meta-analysis indicated that both IMN and DCP can achieve similar fracture union with a similar incidence of radial nerve injury and infection. IMN was associated with an increased risk of shoulder impingement, more restriction of shoulder movement, an increased risk of intraoperative fracture comminution, a higher incidence of implant failure, and an increased risk of re-operation. The overall GRADE system evidence quality was very low, which reduces our confidence in the recommendations of this system. DCP may be superior to IMN in the treatment of humeral shaft fractures. Because of the low quality evidence currently available, high-quality RCTs are required.