Molecular diagnostic panels for enteric pathogens offer increased sensitivity and reduced turnaround time. However, many pathogen detections do not change clinical management, and the cost is substantial.We performed a retrospective chart review of adult outpatients with diarrhea at the University of Virginia who had samples tested by the FilmArray Gastrointestinal Panel (BioFire Diagnostics, Salt Lake City, UT) to identify the clinical yield and to validate the clinical criteria for testing recommended in the 2017 Infectious Diseases Society of America (IDSA) guidelines.We analyzed 629 tests sent from adult outpatients with diarrhea between March 23, 2015, and July 18, 2016. A pathogen was detected in 127 of 629 specimens (20.2%). The most common pathogens were enteropathogenic (47, 7.5%), norovirus (24, 3.8%), enteroaggregative (14, 2.2%), (9, 1.4%), and (9; 1.4%). The clinical yield of testing was low, with antimicrobial treatment clearly indicated for only 18 subjects (2.9%) and any change in clinical management indicated for 33 subjects (5.2%). Following the clinical criteria for diagnostic testing from the 2017 IDSA guidelines, which suggest diagnostic testing for patients with fever, abdominal pain, blood in stool, or an immunocompromising condition, would have reduced testing by 32.3% without significantly reducing the clinical yield (sensitivity, 97.0%; 95% confidence interval [CI], 84.2%-99.9%; negative predictive value, 99.5%; 95% CI, 97.3%-100.0%).The clinical yield of molecular diagnostic testing in this population was low. Compliance with IDSA guidelines in adult outpatients with diarrhea could reduce testing by approximately one-third.