There is limited capacity and infrastructure in sub-Saharan Africa to conduct clinical trials for the identification of efficient and effective new prevention, diagnostic and treatment modalities to address the disproportionate burden of disease. This paper reports on the process to establish locally driven infrastructure for multicentre research and trials in Nigeria known as the Nigeria Implementation Science Alliance Model Innovation and Research Centres (NISA-MIRCs). We used a participatory approach to establish a research network of 21 high-volume health facilities selected from all 6 geopolitical zones in Nigeria capable of conducting clinical trials, implementation research using effectiveness-implementation hybrid designs and health system research. The NISA-MIRCs have a cumulative potential to recruit 60 000 women living with HIV and an age-matched cohort of HIV-uninfected women. We conducted a needs assessment, convened several stakeholder outreaches and engagement sessions, and established a governance structure. Additionally, we selected and trained a core research team, developed criteria for site selection, assessed site readiness for research and obtained ethical approval from a single national institutional review board. We used the Exploration, Preparation, Implementation, Sustainment framework to guide our reporting of the process in the development of this network. The NISA-MIRCs will provide a nationally representative infrastructure to initiate new studies, support collaborative research, inform policy decisions and thereby fill a significant research infrastructure gap in Africa's most populous country.