A systematic top-down procedure to design an effective plantwide control system for economically (near) optimum process operation over a wide throughput range is developed. The proposed procedure focuses on devising a control system for optimal operation at maximum throughput, where usually the highest number of constraints is active and the economic benefits of improved operation are the greatest. To do so, loops for tight control of all the active constraints and economically sound controlled variables (CVs) corresponding to unconstrained degrees of freedom are first implemented (Step 1) followed by a consistent inventory control system (Step 2). This control system is adapted with setpoints that become unconstrained at lower throughputs taking up additional economic CV control or throughput manipulation (Step 3). Iteration between the three steps may be necessary to eliminate fragile/unconventional inventory loops (Step 4). The application of the methodology is demonstrated on three realistic example processes. (c) 2013 American Institute of Chemical Engineers AIChE J, 59: 2407-2426, 2013