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This work addresses the lot-sizing and production scheduling problem of multi-stage multi-product food industrial facilities. More specifically, the production scheduling problem of the semi-continuous yogurt production process, for two large-scale Greek dairy industries, is considered. Production scheduling decisions are made using two approaches: (i) an optimization approach and (ii) a rule-based approach, which are followed by a comparative study. An MILP model is applied for the optimization of short-term production scheduling of the two industries. Then, the same problems are solved using the commercial scheduling tool ScheduleProTM, which derives scheduling decisions using simulation-based techniques and empirical rules. It is concluded that both methods, despite having their advantages and disadvantages, are suitable for addressing complex food industrial scheduling problems. The optimization-based approach leads to better results in terms of operating cost reduction. On the other hand, the complexity of the problem and the experience of production engineers and plant operators can significantly impact the quality of the obtained solutions for the rule-based approach.