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The INSPIRE—Integrating and Scaling Up PMTCT through Implementation REsearch—initiative was established as a model partnership of national prevention of mother-to-child transmission of HIV (PMTCT) implementation research in 3 high HIV burden countries—Malawi, Nigeria, and Zimbabwe. INSPIRE aimed to link local research groups with Ministries of Health (MOH), build local research capacity, and demonstrate that implementation research may contribute to improving health care delivery and respond to program challenges.We used a mixed methods approach to review capacity building activities, as experienced by health care workers, researchers, and trainers conducted in the 6 INSPIRE projects before and during study implementation.Between 2011 and 2016, over 3400 health care workers, research team members, and community members participated in INSPIRE activities. This included research prioritization exercises, proposal development, good clinical practice and research ethics training, data management and analysis workshops, and manuscript development. Health care workers in clinics and district health offices acknowledged the value of hosting implementation research projects and how the quality of services improved. Research teams acknowledged the opportunities that projects provided for personal development and the value of participating in a multicountry research network.INSPIRE provided an opportunity for African-led research in which researchers worked closely with national MOH to identify priority research questions and implement studies. Close partnerships between research teams and local implementers facilitated project responsiveness to local program issues. Consequently, processes and training needed for study implementation also improved local program management and service delivery. Additional benefits included improved data management, publications, and career development.