Background: In January 2019, our large academic medical center implemented hard stops for ordering Clostridiodes difficile nucleic acid amplification testing (NAAT), and required a discussion with an infectious diseases physician if the order was placed in a clinical scenario not consistent with the 2017 IDSA/SHEA C. difficile infection (CDI) testing guidelines. Recently, some groups have expressed concerns that requiring the discontinuation of laxatives may delay the diagnosis of CDI and result in serious adverse outcomes. Methods:C. difficile testing stewardship interventions were performed at 2 hospitals within the same university health system to reduce inappropriate testing. In January 2019, a best practice advisory (BPA) was implemented to alert providers ordering C. difficile NAAT if patients had received laxatives within 24 hours, requiring a discussion with the ID physician to override the hard stop. We reviewed clinical outcomes of patients who had a BPA alert due to laxative use within the past 24 hours April 23 to October 23, 2019. Results: During the study period, there were 235 patients with a BPA because of laxative use within the past 24 hours. Moreover, 55 (23.4%) continued to experience diarrhea after the discontinuation of laxatives and were retested for CDI within 7 days. Only 8 tests returned positive, suggesting that, at most, 3.4% of cases had delayed diagnoses because of the hard stop. This finding is supported by the increase in the percentage of tests positive from 11.6% observed overall to 14.6% (8 of 55) after this intervention. There were no severe CDI cases (ICU admission, colectomy, or death) among patients who had delayed testing due to laxative use. Conclusions: In the setting of laxative use, C. difficile testing stewardship interventions with C. difficile NAAT using a hard-stop BPA are effective in reducing unnecessary testing and safe if they are used in combination with a real-time expert input of the risk of clinical disease.