The efficient operation of many modern industrial unit operations is a fine balancing act between the need to operate as close as possible to the optimal operating conditions, while still having sufficient ability to overcome non-routine process upsets. The need to balance these opposing requirements is most evident when assessing new process control structures for existing unit operations. While there are control performance analysis techniques and assessment methodologies available to assess control structures, these techniques and methodologies do not explicitly calculate the overall economic impact and are also complicated to use. In this manuscript, a novel, versatile methodology is proposed to systematically analyse the expected economic benefits of process control structures taking into consideration their overall impact on plant operations. It is a hierarchical systematic methodology that will identify opportunities to improve economic operations, identify relevant process control structures and finally comprehensively quantify the overall economic benefits of implementing a new control structure versus current operations. This methodological approach employs Net Present Value (NPV) to systematically assess the economic implications while employing process safety/risk analysis concepts developed in the Layer of Protection Analysis (LOPA) to translate process upset information and subsequent control actions into economic consequences that are then used in the NPV analysis. The methodology is then applied to a case study of a high purity methanol distillation unit located in an industrial methanol production plant, where two new process control alternatives were compared against the current operations. Through the case study, it is illustrated how the comprehensive economic information generated by the proposed method can aid an informed decision-making process.