Increasing interest in multimodal breast cancer diagnosis has led to the development of methods for MRI to X-ray mammography registration. The severe breast deformation in X-ray mammography is often tackled by biomechanical models, yet there is no common consensus in literature about the required complexity of the deformation model and the simulation strategy. We present for the first time an automated patient-specific biomechanical model based image registration ofMRI to digital breast tomosynthesis (DBT). DBT provides three-dimensional information of the compressed breast and as such drives the registration by a volume similarity metric. We compare different simulation strategies and propose a patient-specific optimization of simulation and model parameters. The average three-dimensional breast overlap measured by Dice coefficient of DBT and registered MRI improves for four analyzed subjects by including the estimation of unloaded state, simulation of gravity, and a concentrated pull force that mimics manual positioning of the breast on the plates from 88.1% for a mere compression simulation to 93.1% when including all our proposed simulation steps, whereas additional parameter optimization further increased the value to 94.4%.