Deformable registration has been widely used in neuroscience studies for spatial normalization of brain images onto the standard space. Because of possible large anatomical differences across different individual brains, registration performance could be limited when trying to estimate a single directed deformation pathway, i.e., either from template to subject or from subject to template. Symmetric image registration, however, offers an effective way to simultaneously deform template and subject images toward each other until they meet at the middle point. Although some intensity-based registration algorithms have nicely incorporated this concept of symmetric deformation, the pointwise intensity matching between two images may not necessarily imply the matching of correct anatomical correspondences. Based on HAMMER registration algorithm (Shen and Davatzikos, : IEEE Trans Med Imaging 21:1421–1439), we integrate the strategies of hierarchical attribute matching and symmetric diffeomorphic deformation to build a new symmetric-diffeomorphic HAMMER registration algorithm, called as S-HAMMER. The performance of S-HAMMER has been extensively compared with 14 state-of-the-art nonrigid registration algorithms evaluated in (Klein et al., : NeuroImage 46:786–802) by using real brain images in LPBA40, IBSR18, CUMC12, and MGH10 datasets. In addition, the registration performance of S-HAMMER, by comparison with other methods, is also demonstrated on both elderly MR brain images (>70 years old) and the simulated brain images with ground-truth deformation fields. In all experiments, our proposed method achieves the best registration performance over all other registration methods, indicating the high applicability of our method in future neuroscience and clinical applications. Hum Brain Mapp 35:1044–1060, 2014. © 2013 Wiley Periodicals, Inc.