A realistic solar driven membrane distillation desalination system (SMDDS) is expected to be fully functional in the presence of uncertain sunlight radiation and fluctuating freshwater demand. Since these time-variant disturbances and their cumulative effects can often be accommodated with a collection of properly-sized buffer units embedded in a suitable system configuration, a systematic SMDDS design strategy is thus developed in the present study on the basis of a novel quantitative measure. Specifically, a generic mathematical programming model is formulated for computing the temporal flexibility index of any given system. By assessing the operational flexibilities of alternative candidates, the most appropriate design can be identified accordingly. The results obtained in case studies show that the proposed approach is convenient and effective for addressing various operational issues in SMDDS design. (C) 2013 Elsevier B.V. All rights reserved.