EK-181 is a low-activation ferritic/martensitic steel that is an attractive candidate for in-core component materials for both fast reactors and fusion reactors. To assess the effect of microstructural engineering on radiation response, two variants of EK-181 were studied: one in an annealed condition and the other subject to severe plastic deformation. These specimens were irradiated with 3.5 MeV Fe self-ions up to 400 peak displacements per atom (dpa) at temperatures ranging from 400 °C to 500 °C. The deformation did not suppress swelling over the whole irradiated region. Instead, deformed samples showed higher swelling in the near-surface region. Void swelling was found to be correlated with grain boundary instability. Significant grain growth occurred when steady-state void growth started.