OBJECTIVE Interest in intramedullary metacarpal fracture fixation (IMFF) with screws is increasing. However, the optimal screw diameter for fracture fixation is not yet established. In theory, larger screws should be more stable, but there is concern about long-term sequelae of larger metacarpal head defects and extensor mechanism injury created during insertion as well as implant cost. Therefore, the purpose of this study was to compare different diameter screws for IMFF to a popular and more cost-effective alternative of intramedullary wiring. METHODS Thirty-two cadaveric metacarpals were used in a transverse metacarpal shaft fracture model. Treatment groups consisted of IMFF with 3.0 × 60 mm, 3.5 x 60 mm, and 4.5 x 60 mm screws as well as 4 1.1-mm intramedullary wires. Cyclic cantilever bending was performed with the metacarpals mounted at 45° to simulate physiologic loading. Cyclical loading at 10, 20, and 30 N was performed to determine fracture displacement, stiffness, and ultimate force. RESULTS At 10, 20, and 30 N of cyclical loading, all screw diameters tested provided similar stability as measured by fracture displacement and were superior to the wire group. However, ultimate force under load to failure testing was similar between the 3.5- and 4.5-mm screws and superior to 3.0-mm screws and wires. CONCLUSIONS For IMFF, 3.0, 3.5, and 4.5-mm diameter screws provide adequate stability for early active motion and are superior to wires. When comparing the different screw diameters, 3.5- and 4.5-mm diameter screws offer similar construct stability and strength superior to the 3.0-mm diameter screw. Therefore, to minimize metacarpal head morbidity, smaller screw diameters may be preferable. CONCLUSIONS This study suggests that IMFF with screws is biomechanically superior to wires in cantilever bending strength in the transverse fracture model. However, smaller screws may be sufficient to permit early active motion while minimizing metacarpal head morbidity.