Zr/Nb multilayers with periodicities of 10, 30 and 60 nm were prepared by magnetron sputtering and irradiated for prolonged time (1311 h) by γ-rays with energy of 1.25MeV and a dose of 510 kGy. A qualitative comparison between XRD patterns acquired before and after irradiation revealed a progressive increase of compressive stress, especially in Nb layers, for smaller periodicities with a consequent increase in hardness measured by nanoindentation. The combination of smaller grain size and radiationinduced defect density distribution, primarily in Nb layers, was found to be responsible for the observed radiation hardening effect.