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Abstract Nanostructured ferritic alloys (NFAs) having sub-micron grain size with a high density of nano-oxides (NOs) (size of ∼2–3 nm) are one of the best candidates for structural components in Generation IV nuclear systems. In this study, 14YWT NFA cladding tubes were irradiated in BOR60 reactor up to 7 dpa at 360–370 °C. Detailed microstructural analysis has been conducted using bright field transmission electron microscopy, bright field scanning transmission electron microscopy, energy filtered transmission electron microscopy, energy dispersive X-ray spectroscopy, electron energy loss spectroscopy and transmission Kikuchi diffraction techniques. This revealed cavities, <100> and <111> type dislocation loops, and α′ precipitates forming after irradiation with relationships between cavities and NOs, and α′ precipitates and NOs. Cavities mostly form on the NOs; whereas, α′ precipitates form between the NOs where the point defect concentration is high. Moreover, α′ precipitates are distributed homogenously on and around the dislocation loops which is consistent with the observation that there is no Cr segregation on dislocation loops. Grain boundaries were found to be mostly depleted in Cr; however, the characteristics of each grain boundary determines the Cr behavior and the α′ denuded zone around the grain boundaries. Mechanical properties of the irradiated tubes have been determined by using both low force and high force nanoindentation techniques, resulting in 1.03 ± 0.33 GPa and 0.82 ± 0.20 GPa hardening, respectively. Dispersed barrier hardening calculations and nanoindentation measurements are in good agreement. In this study, 14YWT NFA has been systematically studied after neutron irradiation to better understand its superior performance: low α′ concentration, low swelling and low radiation-induced hardening. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]