In this essay we investigate the "lessons learned" within the domain of human and organizational factors (HOF) from operating European nuclear power plants (NPPs) in a fifty-year perspective. Specifically, we consider learning processes at an industry level that aim at promoting human contributions to nuclear safety. This is done by bringing together two main perspectives: (1) a historical perspective on HOF-related institutional and research initiatives is presented by outlining the history of nuclear safety according to three major nuclear accidents, (2) an applied perspective is provided on how HOF are managed in the field. This latter perspective rests on the results of the EU Project LearnSafe, conducted in the European nuclear industry between 2001 and 2004, and its re-evaluation 15 years later by means of an interview study carried out with 21 European managers from the nuclear industry. Our results reveal that the European nuclear industry has to some extent encoded the HOF lessons learned into routines, tools and systems. The three accidents have promoted a broadening of knowledge, ranging from simple ergonomics to crucial issues of interactions between major stakeholders in the nuclear domain. As a conclusion to our study, we suggest that academia and industry should search for improved collaboration, especially in terms of including HOF into safety activities and linking HOF issues to technical design factors and associated hazard potentials. Moreover, we conclude that avoiding major nuclear accidents requires a continuous re-invention of HOF, which should aim to involve and harmonize divergent interests of several stakeholders, demanding further research and efforts to translate insights into practice.