This study investigates the effect of the pilot hole size, implant depth, synthetic bone density, and screw size on the pullout strength of the self-tapping screw using analytical, finite element, and experimental methodologies. Stress distribution and failure propagation mode around the implant thread zone are also investigated. Based on the finite element analysis (FEA) results, an analytical model for the pullout strength of the self-tapping screw is constructed in terms of the (synthetic) bone mechanical properties, screw size, and the implant depth. The pullout performance of self-tapping screws is discussed. Results from the analytical and finite element models are experimentally validated.