Nowadays companies have to face a competitive market that requires small volumes with a high level of customisations. In this context, assembly quality and timeliness is crucial. To guarantee flexibility and personalization, manual operations still have a crucial role for a lot of manufacturing sectors, so that workers’ conditions and ergonomics are important factors to achieve a better product quality and overall cost reduction. Ergonomics evaluation in manufacturing is a challenging and expensive activity that requires a transdisciplinary approach, to merge technical and social sciences to finally have a consolidated and reliable evaluation. This paper compared two digital human simulations tools offered by Siemens Tecnomatix: Jack and Process Simulate. They were applied on the same industrial case study, concerning the hood assembly of an agricultural machine, comparing results on ergonomics reports and usage time. Results confirmed the advantage of adopting a digital approach to predict the human effort and ergonomic risk related to a series of tasks. At the same time, they showed the major strengths and weaknesses of the two analysed tools and defined how they can be successfully adopted by companies. The paper finally provided guidelines to drive companies in choosing the best tool according to their needs.