The buffer allocation problem is an NP-hard combinatorial optimization problem involving the determination of the number of buffers in buffer locations required to increase the efficiency of a production line. Researchers in this field have proposed various optimization techniques to solve the problem for different types of production system configurations. In this study, a hybrid approach-based simulation optimization is proposed to determine the buffer sizes required in open serial production lines to maximize the average production rate of the system. This approach involves the use of a search tool and an evaluative tool. A hybrid approach using a genetic algorithm and simulated annealing is used as a search tool to create candidate buffer sizes. As an evaluative tool, discrete event simulation modeling is used to obtain the average production rate of the line. The performance of the proposed approach and the power of the hybridization are investigated for various serial line configurations. Promising results demonstrate the efficacy of the proposed hybrid approach for the buffer allocation problem in open serial lines. (C) 2015 Elsevier Ltd. All rights reserved.