The worldwide shared definition of "optimal design" refers to the cheapest and simplest design able to perform the required job; most of the time this definition is strictly related to given operating conditions, i.e. the input variables are seldom subjected to considerable variations. However, in process engineering, plenty of cases don't fit this definition due to the uncertain nature of the feedstock needed to be processed. Therefore, if a system is likely to undergo several and substantial perturbations, an a priori flexibility assessment can be crucial for the good performance of the operation. In chemical engineering the leading separation process is distillation. Hence the first purpose of this paper is to define a procedure and compare the different flexibility indexes found in literature in order to perform a simple distillation column flexibility assessment. The second goal of this paper is to couple the flexibility and economic aspects related to the distillation column investment costs and again to compare the different indexes economic behaviours.