Background: Clostridioides difficile (C. difficile) is the primary cause of healthcare-associated infectious diarrhea. Pediatric patients with oncology and stem cell transplant (SCT) diagnoses are at greater risk of C. difficile infections (CDI) and C. difficile colonization than those without. Misdiagnosis of C. difficile colonization as infection and subsequent unnecessary treatment can lead to antibiotic resistance, increased healthcare costs, and an overestimation of CDI rates. Methods: A best practice advisory (BPA) was built into the electronic medical record to guide decision making regarding clinically indicated C. difficile testing. Tests for CDI were to be sent only if the patient met all the predefined clinical criteria for testing. The number of CDI tests ordered per 1,000 patient days, the number of tests positive per 1,000 patient days, and the proportion of positive tests were compared before and after implementation. Results: The number of tests ordered per 1,000 patient days declined from 8.2 to 5.7 after the intervention. Positive tests per 1,000 patient days increased from 2.2 to 3.5 after the intervention. This demonstrates an increase in the proportion of positive tests from 27% to 61%. Discussion: This intervention led to fewer CDI tests ordered, but CDI incidence and test positivity proportion increased. This is likely reflective of better-targeted testing for CDI and the identification of true-positive cases of infection, but we cannot rule out a coincident increase in CDI activity during the study period. Through education and electronic reminders of the clinical indicators for testing for CDI, the frequency of testing for C. difficile was reduced.