Registration of lung CT images acquired at different respiratory phases is clinically relevant in many applications, such as follow-up analysis, lung function analysis based on mechanical elasticity, or pulmonary airflow analysis, etc. In order to find accurate and reliable transformation for registration, a proper choice of dissimilarity measure is important. Even though various intensity-based measures have been introduced for precise registration, the registration performance may be limited since they mainly take intensity values into account without effectively considering useful spatial information. In this paper, we attempt to improve the non-rigid registration accuracy between exhale and inhale CT images of the lung, by proposing a new dissimilarity measure based on gradient orientation representing the spatial information in addition to vessel-weighted intensity and normalized intensity information. Since it is necessary to develop non-rigid registration that can account for large lung deformations, the B-spline free-form deformation (FFD) is adopted as the transformation model. The experimental tests for six clinical datasets show that the proposed method provides more accurate registration results than competitive registration methods.