Biodegradable metals represent a valuable solution for the development of temporary vascular implants. These are expected to dissolve in the body over time, avoiding side effects typical of permanent implants, such as thrombosis, in-stent restenosis and chronic inflammation. Iron (Fe)-based alloys, such as iron–manganese (Mn) alloys, are of particular interest for cardiovascular applications due to their intrinsic properties. However, their degradation behavior and biological performance need to be improved. Femtosecond (fs)-laser-induced surface topography could affect both their degradation and cell–material interaction. In this work, fs-laser-induced patterning was performed on a Fe–Mn20 alloy to tune both the degradation behavior of the material and its interaction with the biological environment for cardiovascular applications. Processing parameters were varied to select an optimized surface morphology, characterized by linear grooves. Profilometric analysis, scanning electron microscopy and degradation rate analysis were performed on the treated samples. Thereafter, endothelial cell viability tests and hemocompatibility assessment were carried out on selected process conditions. The obtained fs-laser-induced linear patterns were demonstrated to decrease the degradation rate and to improve the biological response toward both endothelial cells and blood. These results demonstrate how fs-laser-induced patterning is a promising solution for the development of biodegradable metal-based vascular implants.