Fouling and aging are the main causes for the degradation of heat exchanger performance from a well-behaved heat-transfer performance. They result in extra capital and energy costs for heat exchanger networks (HENs) to compensate for the gap in target temperatures. To reduce the negative effect of deposition, this paper presents a novel methodology for managing the cleaning schedule problem in the design of HENs. The method consists of three steps. First, obtain an original HEN using pseudotemperature enthalpy diagram approach. Then, simplify the structure of the original HEN through loop-breaking and small size unit eliminating strategies. Finally, optimize heat-transfer areas and cleaning schedules by considering the growth of deposits via a mixed integer nonlinear programming model. Therefore, the model is capable of weighing the capital cost for exchangers and the operation cost for both utility consumption and cleaning activities. In this study, two off-line cleaning alternatives with distinct cleaning efficiencies are provided for deposition removal; therefore, the problem of which method should be selected for each exchanger will also be investigated in the model. At the end of the study, an illustrative example is presented to demonstrate the proposed method. The results have indicated the potential for cost savings when good cleaning schedules are planned with the design of HENs.