Lead thick rubber bearings (LTRBs) are capable of mitigating vertical subway-induced vibration and horizontal seismic force as well as adding supplementary damping. During earthquakes, LTRBs would be accompanied by lateral displacements, which would cause vertical stiffness reduction. However, much uncertainty still exists about quantifying this reduction of vertical stiffness. This research intends to investigate the influence factors of the vertical stiffness reduction of LTRBs and to develop a formulation for accurate prediction. Three full-scale LTRBs with different first and second shape factors (S1 and S2) were designed and subjected to combined lateral displacement and compressive load for determining their vertical stiffness. Based on material and isolator level tests, a finite element (FE) model of LTRBs was calibrated. Then, parametric FE analyses were performed to explore the effects of various parameters on the normalized vertical stiffness over a wide range of lateral offset. Experimental and numerical studies quantified the reduction of vertical stiffness for different values of vertical pressure, S1, and S2. Besides, the test and simulated results were compared to the results from existing formulations and the inaccuracy of these formulations was indicated. Finally, a new formulation was developed and it showed good agreement with experimentally and numerically determined vertical stiffness of LTRBs.