In recent years, increasing concern of process economics, strict product specifications, and stringent safety and environmental regulations has resulted in increased use of material recycle and energy integration in chemical process plants. These highly integrated plants need effective control systems for smooth and optimal operation. This has led researchers to propose plant-wide control (PWC) system design methodologies. The present contribution considers the application of one such recently proposed methodology, the integrated framework of simulation, heuristics, and optimization (IFSHO) [Vasudevan, S.; Rangaiah, G. P. Integrated Framework Incorporating Optimization for Plant-Wide Control of Industrial Processes. Ind. Eng. Chem. Res. 2011, 50, 8122−8137]. This framework is applied to the autorefrigerated alkylation process for the production of high-octane C8 components, which is important in petroleum refining. The step-by-step application of IFSHO is discussed. The performance of the resulting control structure is analyzed and compared to that of the earlier control structure [Luyben, W. L. Design and Control of an Autorefrigerated Alkylation Process. Ind. Eng. Chem. Res. 2009, 48, 11081−11093], using several performance assessment criteria.