Vibration control is the key to development of high-speed and light-weight transmission system. There are many factors affecting the vibration, and the influence of misalignment is the most obvious. Therefore, it is important to understand the dynamic response of transmission shaft with misalignment. In previous studies, researchers studied the influence of plane angle misalignment. However, there are few researches on the effect of spatial misalignment on shafting vibration. In this paper, a numerical model of shafting with spatial misalignment is established. The influence of plane angle misalignment and spatial angle misalignment on the vibration is studied. The numerical and experimental results show that the vibration of shafting with spatial angle misalignment is bending-torsional coupled vibration, and the two kinds of vibration reinforce each other, and the torsional vibration is the main vibration. Compared with the influence of plane angle misalignment, the influence of spatial angle misalignment is more obvious..