Printed circuit heat exchangers (PCHEs) have a high heat transfer coefficient which makes them a suitable option for very high temperature reactors (VHTRs). ASME Section VIII design code provide PCHE design rules for non-nuclear applications. The PCHE design methodology for nuclear applications is yet to be established. Towards developing the ASME Section III code rules, this study started with the PCHE design as per section VIII. An experimental set up is developed to evaluate the designed PCHE for creep and creep-fatigue performances. This study performed pretest finite element analysis to estimate experimental responses and failure loads for setting up the experiments. Three dimensional isothermal analyses of the PCHE’s were conducted by using an advanced unified constitutive model to simulate the creep-fatigue interaction. The sub-modeling technique was used to analyze the channel scale response of the PCHE. Analysis results indicate that the failure may be governed by the channel corner responses, which is influenced by the creep-fatigue interaction. Analysis based creep-fatigue damage curve is plotted as per ASME code to evaluate the design of PCHEs for nuclear application.