Abstract A systematic procedure is presented for the synthesis of flexible heat exchanger networks that involve specified uncertainties in the flowrates and inlet temperatures of the process streams. The problem is decomposed into two stages: (i) prediction of matches (ii) derivation of the network configuration. At each stage, synthesis techniques are combined with a flexibility analysis to test the feasibility of operation of the design over the specified range of the uncertain parameters. It is shown that special properties can be exploited to efficiently perform the flexibility analysis. Two examples are given to illustrate the application of the proposed strategy.