The National Institutes of Health (NIH) asked the National Academies of Sciences, Engineering, and Medicine to conduct a quadrennial review of its Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs, in accordance with a legislative mandate. Using quantitative and qualitative analyses of data, this report reviews the operations and outcomes stemming from NIH's SBIR/STTR awards. Drawing on published research and conducting new analyses based on both publicly available data and applicant data provided by NIH, Assessment of the SBIR and STTR Programs at the National Institutes of Health analyzes (1) the effectiveness of NIH's processes and procedures for selecting SBIR and STTR awardees, (2) the effectiveness of NIH's outreach to increase SBIR and STTR applications from small businesses that are new to the programs, from underrepresented states, and from woman-owned and minority-owned businesses, (3) collaborations between small businesses and research institutions resulting from the programs, and (4) a range of direct economic and health care impacts attributable to the programs.