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Modern production systems must guarantee high performance. Increasingly challenging international competition, budget reductions for the health sector and constant technological evolution are just three of the many aspects that drive pharmaceutical companies to continuously improve the productivity of their lines. The scientific literature has for many years been proposing calculation models for estimating the productivity of a machine. One of the most famous, and still used, is overall equipment effectiveness (OEE). This allows the calculation the valuable output considering the six ‘big losses’. The limitations of this approach are noticeable when considering a production line instead of a single machine. Numerous researchers have proposed alternative methods or changes in OEE, to be able to cover the widest spectrum of possible cases. In this study, we wanted to evaluate how such theoretical models related to OEE are actually able to represent the world of tight production flows or whether, in these cases, a more complex type of simulation should be preferred. To do this, we carried out a case study of a production line in the pharmaceutical industry, and the results showed that the simulation approach gives better results because of the peculiarities not considered by the theoretical models.