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Background and Objectives: The contribution of blood establishments (BEs) on Research, Development, and Innovation (R + D + I) is minimally addressed in the literature. Herein, we present an analysis of key indicators of R + D + I in BEs and discuss the impact of their R + D + I interests and priority areas, resources, and outcomes on the delivery of quality health products and services. Methods: Data from a worldwide representation of BEs were collected and analyzed in 2020. We assessed R + D + I areas studied, budget allocations, collaborations with other institutes, number of research staff available, and scientific production of BEs. Results: Details of 15 BEs from four continents were included in the study. All of them conducted R + D + I on a better understanding of their products and product safety. Other areas focused on were donors and donations (87%), bone marrow transplantation (80%), transfusion practices (80%), and immunogenetics (80%). 1%–11% (median of two points five %) of staff and 35–238 (median of 70, n = seven) in number, were involved in R + D + I. In 2018–2019, the budget allocated for R + D + I varied from € two point 6 to €13.7 million (median €seven point 6 million, n = 8) and it was zero point eight–10.5% (median of two points one %) of the total budget of BEs. Twelve (80%) and 11 (73%) BEs collaborated with academic institutes and hospitals, respectively. All centers generated publications and conference presentations, whereas only 4 (27%) hold patents. Conclusion: Research is an essential component in BEs that further potentiates R + D + I by partnering with research centers and universities as well as establishing specialized networks. A strong commitment to allocate resources and establish dedicated facilities or strategic alliances may generate world-class innovations in this ever-growing field.