This paper investigates how the characteristics of operational processes—systematic and project-based—affect the impact of adopting the safety management systems on different performance metrics. The proposed approach allows the development of a framework which matches safety problems and risks encompassed by organizational tasks with solutions generated by new safety knowledge linked to the adoption of the OHSAS 18001 standard. Our analysis of the effect over work accidents, as well as operational and economic performance of implementing the OHSAS 18001 in Spanish manufacturing, construction and professional services organizations during 2006–2009 shows that organizations modify existing safety practices to mitigate work accidents, and that safety learning effects widely vary across industry sectors. Organizations whose current knowledge is mostly codified and processes are highly systematic benefit more from safety knowledge and experience, whereas the effects of the OHSAS 18001 dilute in organizations whose knowledge is high in tacitness, and whose processes difficult the visibility of the consequences of work accidents. This study has important implications for managing knowledge acquisition processes. The findings offer valuable insights on how managers can develop communication and coordination actions to cope with the potential incompatibilities between safety management systems, the properties of knowledge and work environmental conditions.