The objective of the current study was to compare quantitative data on the biomechanical analysis of different techniques for fixation of intercalary bone defects of the humerus, by means of consistently applied methodology on composite models. A total of 25 humeral specimens of composite models were used. An intercalary defect was created and reconstructed using plates, intramedullary nails, external fixators and segmental prosthetic implants. The specimens were loaded under axial compression, four-point bending and torsion within the linear elastic region. Modular segmental implants and intramedullary nails were able to compensate significantly greater amounts of compressive loads compared to locking plates and external fixators. However, in flexion and torsion, the modular segmental implants and the external fixators were significantly better load-bearing devices compared to the intramedullary nails and plates. Early mobilization of the upper limb in patients with diaphyseal bone defects of the humerus could probably be more safe and tolerable when reconstructed with modular segmental implants.