Background This study evaluates the stiffness of both 4.5 mm dynamic compression plates (DCP) and 3.5 mm hybrid locking-compression plates (LCP) for treatment of humeral shaft fractures in a simulated weight bearing model. Methods Testing was performed on 16 4th generation Sawbones humeri. Initial axial and torsional stiffness were determined. Plates were placed and a 5 mm defect was produced. Specimens were subjected to 90,000 loading cycles to simulate 90 days of crutch walking and then loaded to failure. Statistical analysis was performed using a t-test with significance at P < 0.05. Findings Comparison reveals a significant difference between the intact axial and torsional stiffness of 4.5 mm DCPs and 3.5 mm LCPs. The 3.5 mm plates provided 80% of the axial stiffness and 75% of the torsional stiffness of the 4.5 mm plates. The 3.5 mm plated bones failed at 79% of the mean failure load of the 4.5 mm plated bones. The 3.5 mm plated bones failed due to incidental torsion during axial loading; the 4.5 mm plated bones failed as a result of gap closure. Interpretation Our results followed expectations due to differences in plate dimensions. There were no apparent differences between constructs following cyclic loading. Our model includes a fracture gap, which requires the plate to carry the entire load. This does not simulate the actual clinical scenario wherein healing would tend to improve construct performance. While the constructs performed differently, both appear to support loads that are anticipated in the clinical setting.