Pragmatic clinical trials are used to test the efficacy of interventions in a real-world clinical practice setting. The purpose of this article was to summarize the presentation given at the Council on Advancement of Nursing Science 2017 Meeting. Key science focus areas of the National Institute of Nursing Research (NINR) and the National Institutes of Health (NIH) guidelines relevant to pragmatic clinical trials were reviewed. The NIH supports some large-scale pragmatic trials and NINR participates in two of them. Generally, the NINR supports small-scale pragmatic trials that are a mission fit with the NINR. Now pragmatic trials are subject to the new NIH clinical trial requirements. Investigators must respond to a specific clinical trial announcement and use the new clinical trial application forms. The NINR program staff are a valuable resource to answer questions that investigators may have regarding their pragmatic clinical trial proposal. Published by Elsevier Inc.