Africa was previously insufficiently represented in the emerging discipline of biobanking despite commendable early efforts. However, with the Human, Heredity, and Health in Africa (H3Africa) initiative, biorepository science has been bolstered, regional biobanks are springing up, and awareness about biobanks is growing on the continent. The Stroke Investigative Research and Educational Network (SIREN) project is a transnational, multicenter, hospital and community-based study involving over 3000 cases and 3000 controls recruited from 16 sites in Ghana and Nigeria. SIREN aims to explore and unravel the genetic and environmental factors that interact to produce the peculiar phenotypic and clinical characteristics of stroke as seen in people of African ancestry and facilitate the development of new diagnostics, therapeutics, and preventative strategies. The aim of this article is to describe our experience with the development of the procedure for collection, processing, storage, and shipment of biological samples (blood, serum, plasma, buffy coat, red cell concentrates, and DNA) and brain imaging across coordinating and participating sites within the SIREN Project. The SIREN network was initiated in 2014 with support and funding from the H3Africa Initiative. The SIREN Biobank currently has 3015 brain images, 92,950 blood fractions (serum, plasma, red cell concentrates, and buffy coat) accrued from 8450 recruited subjects, and quantified and aliquoted good-quality DNA extracts from 6150 study subjects. This represents an invaluable resource for future research with expanding genomic and trans-omic technologies. This will facilitate the involvement of indigenous African samples in cutting-edge stroke genomics and trans-omics research. It is, however, critical to effectively engage African stroke patients and community members who have contributed precious biological materials to the SIREN Biobank to generate appropriate evidence base for dealing with ethical, legal, and social issues of privacy, autonomy, identifiability, biorights, governance issues, and public understanding of stroke biobanking in the context of unique African culture, language, and belief systems.