New federal policies require single IRB review for multisite studies, but many questions remain about how these IRBs will use local knowledge. The findings from our study, the first to examine how single IRBs perceive needs for local knowledge, reveal several challenges. Study respondents identified four potentially relevant types of local knowledge: about culture and linguistics, about geography and socioeconomics, about the researchers, and about the institutions. Such knowledge can potentially be obtained through local sites, but single IRBs may be unaware of potentially relevant local information, and lack of informal relationships may impede single IRBs’ reviews and interactions with researchers. While a recent, commonly used, standardized single‐IRB form asks three basic questions about local information, our findings suggest potential needs for additional information and, thus, have important implications for practice, policy, and research.