Finite element (FE) modelling based on data from three-dimensional high-resolution computed tomography (CT) imaging systems provides a non-invasive method to assess structural mechanics. Automated mesh generation from these voxel based image data can be achieved by direct conversion to hexahedron elements, however these model representations have jagged edges. This paper proposes an automated method to generate smoothed FE meshes from voxel-based image data. Mesh fairing processes are utilized that allow constraints that control the smoothing process, and are computationally efficient. Surfaces of the mesh on the exterior, as well as interfaces between two tissues, can be smoothed by varying fairing parameters and constraint criteria. The method was tested on a variety of real and simulated three-dimensional data sets, resulting in both hexahedron and tetrahedron meshes. It was shown that the fairing process is linearly related to the number of smoothing iterations, and that peak stresses are reduced in FE simulations of the smoothed models. Although developed for micro-CT data sets, this fast and reliable mesh smoothing method could be applied to any three-dimensional image data where node and element connectivity have been defined.