In this paper, a Statistical Model of Deformation (SMD) that captures the statistical prior distribution of high-dimensional deformations more accurately and effectively than conventional PCA-based statistical shape models is used to regularize deformable registration. SMD utilizes a wavelet-based representation of statistical variation of a deformation field and its Jacobian, and it is able to capture both global and fine shape detail without overconstraining the deformation process. This approach is shown to produce more accurate and robust registration results in MR brain images, relative to the registration methods that use Laplacian-based smoothness constraints of deformation fields. In experiments, we evaluate the SMD-constrained registration by comparing the performance of registration with and without SMD in a specific deformable registration framework. The proposed method can potentially incorporate various registration algorithms to improve their robustness and stability using statistically-based regularization.