Background: Single large-fragment plate constructs currently are the norm for internal fixation of middiaphyseal humerus fractures. In cases where humeral size is limited, however, dual small-fragment locking plate constructs may serve as an alternative. The mechanical effects of different possible plate configurations around the humeral diaphysis may be important, but to our knowledge, have yet to be investigated. Questions/purposes: We used finite element analysis to compare the simulated mechanical performance of five different dual small-fragment locking plate construct configurations for humeral middiaphyseal fracture fixation in terms of (1) stiffness, (2) stress shielding of bone, (3) hardware stresses, and (4) interfragmentary strain. Methods: Middiaphyseal humeral fracture fixation was simulated using the finite element method. Three 90 and two side-by-side seven-hole and nine-hole small-fragment dual locking plate configurations were tested in compression, torsion, and combined loading. The configurations chosen are based on implantation using either a posterior or anterolateral approach. Results: All three of the 90 configurations were more effective in restoring the intact compressive and torsional stiffness as compared with the side-by-side configurations, resulted in less stress shielding and stressed hardware, and showed interfragmentary strains between 5% to 10% in torsion and combined loading. Conclusions: The nine-hole plate anterior and seven-hole plate lateral (90 apart) configuration provided the best fixation. Our findings show the mechanical importance of plate placement with relation to loading in dual-plate fracture-fixation constructs. Clinical Relevance: The results presented provide novel biomechanical information for the orthopaedic surgeon considering different treatment options for middiaphyseal humeral fractures.