It is important to be able to predict the creep life of materials used in power plants. This paper illustrates the inadequacies of the Orr–Sherby–Dorn (OSD) creep model in achieving this aim for 2.25Cr–1Mo steel. This failure is explained in terms of non-constant model parameters—which in turn is the result of changing creep mechanisms. The paper introduces a semi-parametric estimation procedure for a variant of the OSD model (a structural coefficients version) that can be used to deal with such changing creep mechanisms while maintaining the structure of the model and consequently producing more reliable long-term predictions compared to the unmodified OSD model and the recently introduced LOESS technique. For 2.25Cr–1Mo steel, it was found that the model parameters varied in line with changing creep mechanisms, but in a modified way compared to that already suggested in the literature for this material. The models used suggested that with diminishing stress and increasing temperature, dislocation creep within the crystal structure morphs into grain boundary dislocation motion and finally Nabarro-Herring creep.