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Reactor pressure vessel (RPV) is one of the key equipment for nuclear power plant, and long-term exposure to high temperature is an important factor causing its performance deterioration. Under core meltdown conditions, RPV steel experiences high temperature creep due to the In-Vessel Retention (IVR) mitigation measures. This paper aims to investigate high-temperature mechanical properties, especially for the creep behaviors of 16MND5 steel after thermal aging at 650 °C for 2000 h. The results showed that the yield stress and ultimate tensile strength of the 16MND5 steel are decreased, and the creep rupture time is rapidly shortened after thermal aging. The microstructure was analyzed by scanning and transmission electron microscopy (SEM, TEM). 16MND5 steel showed a typical bainitic phase before thermal aging. After 2000 h of thermal aging, the micro-grains were coarsened, and finally changed into a ferritic microstructure. Based on Larson-Miller (LM), Orr-Sherby-Dorn (OSD) parameters methods and Kachanov-Rabotnov (K–R) model to predict uniaxial creep life after thermal aging, the prediction results are satisfactory, and all within the double tolerance band. This work reveals the creep damage mechanism of 16MND5 steel after thermal aging, and provides basic data for the implementation of IVR strategy in nuclear power plants after long-term service. • Characterization of creep behaviors are achieved for 16MND5 steel before and after thermal aging. • Creep failure mechanism of thermal aged 16MND5 steel is explained by microscopic observation. • Influence of thermal aging on macro- and micro-creep failure of 16MND5 steel is understood in depth. • Creep life is well predicted by Larson-Miller and Orr-Sherby-Dorn parameters methods, and validated by experiment. • The K–R model accurately characterizes the three creep stages of thermal aged 16MND5 steel. [ABSTRACT FROM AUTHOR]