Process integration is motivated from economic benefits, but it also impacts on the plant behavior introducing interactions and in many cases making the process more difficult to control and operate. A prerequisite for optimal operation is that the HEN is sufficiently flexible, i.e. it must have the ability to operate over a range of conditions while satisfying performance specifications. In this work it is defined the Operational Flexibility related not only to the operating range but also to the costs involved to put the HEN into operation. In order to provide an appropriated metric, the operational flexibility index is defined. Five different networks structures designed for the nominal conditions of a case study are used to illustrate the proposed ideas. It was noticed that a great feasible region does not point out the more economic operation, and the costs must be considered together with the flexibility analysis. These characteristics are taken into account by the novel proposed operational flexibility index, which can also consider during the analysis the increasing in the utility duties, extra utility exchangers and bypass installation. These results clearly point out for the need of a simultaneous framework for flexible design and profitability.