In November 2010, The Office of Behavioral and Social Sciences Research (OBSSR) of the National Institutes of Health (NIH) commissioned the leadership team of John W. Creswell, Ann Klassen, Vicki L. Plano Clark, and Katherine Clegg Smith to develop a resource that would provide guidance to NIH investigators on how to rigorously develop and evaluate mixed methods research applications. Pursuant to this, the team developed this report of “best practices” following three major objectives. To develop practices that: assist investigators using mixed methods as they develop competitive applications for support from NIH; assist reviewers and staff for review panels at NIH who evaluate applications that include mixed methods research; and provide the Office of Behavioral and Social Sciences Research (OBSSR), and the NIH Institutes and Centers, with “best practices” to use as they consider potential contributions of mixed methods research, select reviewers, plan new initiatives, and set priority areas for their science.