Biomaterial direct-write technologies have been receiving more and more attention as rapid prototyping innovations in the area of tissue engineering, regenerative medicine, and biosensor∕actuator fabrication based on computer-aided designs. However, cell damage due to the mechanical impact during cell direct writing has been observed and is a possible hurdle for broad applications of fragile cell direct writing. The objective of this study is to investigate the impact-induced cell mechanical loading profile in cell landing in terms of stress, acceleration, and maximum shear strain component during cell direct writing using a mesh-free smooth particle hydrodynamic method. Such cell mechanical loading profile information can be used to understand and predict possible impact-induced cell damage. It is found that the cell membrane usually undergoes a relatively severe deformation and the cell mechanical loading profile is dependent on the cell droplet initial velocity and the substrate coating thickness. Two important impact processes may occur during cell direct writing: the first impact between the cell droplet and the substrate coating and the second impact between the cell and the substrate. It is concluded that the impact-induced cell damage depends not only on the magnitudes of stress, acceleration, and∕or shear strain but also the loading history that a cell experiences.