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Steel components in the boilers of nuclear reactors are subject to high temperatures and varying loading conditions. This can introduce time-dependent and time-independent plasticity, which can interact with one another. Specimens of 316H austenitic stainless steel were heated to 550 °C and tensile pre-strained to 8%, 11% and 14% followed by 200 h, 280 MPa creep tests. These tests showed an increase in creep resistance with increasing tensile pre-strain. Macroscale simulations using RCC-MR deformation laws proved ineffective at predicting this interaction. Microscale crystal plasticity simulations proved effective at predicting the trends observed experimentally, hence demonstrating the potential of crystal plasticity as a predictive tool for structural integrity analysis.