Fe-based materials are of interest for use in biodegradable implants. However, their corrosion rate in the biological environment may be too slow for the targeted applications. In this work, sandblasting is applied as a successful surface treatment for increasing the degradation rate of pure iron in simulated body fluid. Two sandblasting surfaces with different roughness present various surface morphologies but similar degradation products. Electrochemistry tests revealed that sandblasted samples have a higher corrosion rate compared to that of bare iron, and even more noteworthy, the degradation rate of sandblasted samples remains significantly higher during long-term immersion tests. On the basis of our experimental results, the most plausible reasons behind the fast degradation rate are the special properties of sandblasted surfaces, including the change of surface composition (for the early stage), high roughness (occluded surface sites), and high density of dislocations. Furthermore, the cytocompatibility was studied on sandblasting surfaces using human osteoblast-like cells (MG-63) by indirect and direct contact methods. Results revealed that sandblasting treatment brings no adverse effect to the growth of MG-63 cells. This work demonstrates the significant potential of sandblasting for controlling the degradation behavior of iron-based materials for biomedical applications.