Flow splits and manifolds are encountered in many industrial processes such as heat recovery systems to feed reactant streams and take out product streams. Depending on the application, the flow distribution among the several outlets may be equal or unequal. In this paper we describe a computational method for achieving desired flow distribution in a flow manifold using optimally positioned guide plates. For multiple outlet streams, determining the orientation of the guide plates is a non-trivial problem. The positioning of one guide plate will have an effect on the flow rate through the other outlets. This effect cannot be estimated from simple models but can be calculated using computational fluid dynamics (CFD) simulation of the corresponding flow problem. However, a conventional CFD simulation cannot predict the optimal location of the guide plates. In view of this, we pose the flow distribution problem as a constrained optimization problem and use a well-established algorithm coupled to a computational fluid dynamics (CFD)-based flow solver to develop an automated procedure for the optimal positioning of the guide plates. The robustness of the procedure is illustrated for both equal and unequal flow distributions in a one-inlet, four-outlet manifold with guide plates of fixed and variable lengths. © 2014 Elsevier Ltd. All rights reserved.