Large multinational firms (LMF) play a crucial role in the dynamics of knowledge production worldwide. The study conducted by Université Eiffel, using inventive activities as a central marker, highlights in particular four major results: (i) Large groups represent 80% of worldwide international inventive activities and, contrary to many expectations, this role has increased over the last decade. (ii) Though LMF are present in 60% of inventive metropolitan areas, the top 100 metropolitan areas worldwide concentrate 80% of LMF international patents. (iii) Large metropolitan areas gather 90% of international patents in Asia, 70% in the US, but only 37% in Europe. Europe has thus a very different structure where inventive activities are more distributed with a central role of medium-size metropolitan areas. (iv) ‘National’ LMF play a majority role in the overall production of metropolitan areas: over 90% in Asia, and 75% in the US. In Europe, this share is only 57%. This highlights the role of LMF from other European countries (23%) and from outside of Europe (20%). These four results question research and innovation policies and call for an open debate about their policy-mix and their role in distributive and inclusion objectives. The study has been conducted, using in an integrated way the three major resources developed within RISIS: CIB dataset on large firms, RISIS patent database on patents, and CORTEXT geolocation on metropolitan areas.