The evaluation of the quality and usefulness of climate modeling systems is dependent upon an assessment of both the limited predictability of the climate system and the uncertainties stemming from model formulation. In this study a methodology is presented that is suited to assess the performance of a regional climate model (RCM), based on its ability to represent the natural interannual variability on monthly and seasonal timescales. The methodology involves carrying out multiyear ensemble simulations (to assess the predictability bounds within which the model can be evaluated against observations) and multiyear sensitivity experiments using different model formulations (to assess the model uncertainty). As an example application, experiments driven by assimilated lateral boundary conditions and sea surface temperatures from the ECMWF Reanalysis Project (ERA-15, 1979–1993) were conducted. While the ensemble experiment demonstrates that the predictability of the regional climate varies strongly between different seasons and regions, being weakest during the summer and over continental regions, important sensitivities of the modeling system to parameterization choices are uncovered. In particular, compensating mechanisms related to the long-term representation of the water cycle are revealed, in which summer dry and hot conditions at the surface, resulting from insufficient evaporation, can persist despite insufficient net solar radiation (a result of unrealistic cloud-radiative feedbacks).