In this work, we address the problem of optimizing corn-based bioethanol plants through the use of heat integration and mathematical programming techniques. The goal is to reduce the operating costs of the plant. Capital cost, energy usage, and yields-all contribute to production cost. Yield and energy usage also influence the viability of corn-based ethanol as a sustainable fuel. We first propose a limited superstructure of alternative designs including the various process units and utility streams involved in ethanol production. Our objective is to determine the connections in the network and the flow in each stream in the network such that we minimize the energy requirement of the overall plant. This is accomplished through the formulation of a mixed-integer nonlinear programming problem involving short-cut models for mass and energy balances for all the units in the system, where the model is solved through two nonlinear programming subproblems. We then perform a heat integration study on the resulting flowsheet; the modified flowsheet includes multieffect distillation columns that further reduces energy consumption. The results indicate that it is possible to reduce the current steam consumption required in the transformation of corn into fuel grade ethanol by more than 40% compared to initial basic design. (C) 2008 American Institute of Chemical Engineers.