This paper investigates the effects of repeated stress relaxation loadings and post stress relaxation creep to assess the stress relaxation–creep interaction and microstructural evolution of 2.25Cr–1Mo steel. Prior to creep testing, the microstructure of the material subjected to stress relaxation exhibited a structure which was non-conservative in predicting the remaining creep life of the material. The results obtained in the test program showed that the damage due to the effects of stress relaxation was crucial and had a significant effect on the creep life of this material. The study has also shown that the extent of metallurgical degradation, due to stress relaxation, may not be evident through microstructural assessment. Consequently, established life assessment procedures may not represent conservative estimates of remaining life because the microstructural indicators of damage, due to stress relaxation, are not evident. The effects of stress relaxation on the creep properties of ferritic pressure vessel steel are life limiting for critical high temperature power generation plant. In this study a comprehensive test program has been undertaken to assess the interaction of stress relaxation with creep and microstructural evolution in 2.25Cr–1Mo steel.