•A procedure for the estimation of the lifetime reduction is proposed.•The plant dynamic model is the core of the proposed procedure.•A three pressure level combined cycle power plant is selected as test case.•Different transient conditions are analyzed.•The lifetime reduction of the high pressure superheater and drum is computed. The liberalization of the European energy markets combined with the rapid spread of unpredictable renewable energy sources have stressed the need of improving the traditional power units flexibility. Fast start-ups/shut downs and rapid load variations have become priority objectives because they guarantee high profits in the short term but cause a lifetime reduction due to thermo-mechanical fatigue, creep and corrosion. To this purpose, in the present work, an innovative procedure, able to predict the power plant dynamic behaviour during load variations, identify the most stressed components and estimate their lifetime reduction is presented and tested. Being combined cycles the most efficient, flexible and widespread technologies, the selected test case is a 380MW combined cycle unit. To predict the plant dynamic performance a dynamic model has been built in Modelica language and several transient conditions investigated. The high pressure steam drum and superheater are the most stressed components. Results show a 52.9% reduction in superheater collectors life if the load variation is 50% faster than the reference case. On the contrary, a 35.8% lifetime increase is observed if the load variation is 50% slower. For the same conditions the high pressure steam drum life is reduced by 31.9% and increased by 16.3%, respectively. Also the superheater tube bank lifetime reduction is computed. The proposed procedure can be considered a valuable innovative tool to assist power plant designers and operators.