In this study, a mask-less laser-assisted patterning method is used to fabricate well-defined cell-adhesive microdomains delimited by protein-repellent poly(ethylene glycol) (PEG) microstructures prepared from multiarm (8-PEG) macromonomers. The response of murine fibroblasts (L-929) toward these microdomains is investigated, revealing effective cell confinement within the cell-adhesive areas surrounded by nonadhesive 8-PEG microstructures. Moreover, the spatial positioning of cells in microdomains of various sizes and geometries is analyzed, indicating control of cell density, size, and elongated cell shape induced by the size of the microdomains and the geometric confinement.