Background:Clostridioides difficile infection (CDI) accounts for >500,000 community-, nursing-, and hospital-acquired infections (HAIs), as well as 15,000–30,000 deaths, and =$4.8 billion in the United States annually. C. difficile toxin B gene nucleic acid amplification testing (NAAT) cannot distinguish between active CDI and colonization, particularly in the setting of laxative use or enteral feeding. Lack of judicious testing can result in the incorrect diagnosis of CDI, unnecessary CDI treatment, increased costs, and falsely augmented HAI rates. Like many healthcare facilities, the VA San Diego Healthcare System (VASDHS) solely utilizes C. difficile NAAT for CDI diagnosis. The aim of this study was to implement and evaluate a facility-wide initiative at the VASDHS to reduce healthcare onset, healthcare facility associated CDI (HO-HCFA CDI), including the use of a test ordering algorithm. Methods: From fiscal year (FY) 2015–2018, various measures were implemented including a hand hygiene initiative, reduction in fluoroquinolone usage, prompt isolation of patients with CDI, thorough terminal cleaning of rooms, and, lastly, a test-ordering algorithm starting FY2018. A retrospective study was performed to assess VASDHS HO-HCFA CDI case incidence, risk factors for infection, laxative or enteral feeding use at the time of testing, and CDI treatment. Results: Patient demographic data, medical history, CDI history, laxative use, treatment, and cost of CDI treatment were reviewed. From 2015 to 2018, 127 cases of HO-HCFA CDI were identified. The total number of HO-HCFA CDI cases and medication cost for CDI treatment were dramatically reduced from 2017 to 2018 following implementation of the test-ordering algorithm (Table 1, Fig. 1). This trend corresponded to a significant reduction in median HO-HCFA CDI cases per month (P = .02), medication cost of CDI treatment (P = .02), and proton pump inhibitor (PPI) use at the time of testing (P = .01). The number of positive HO-HCFA CDI cases associated with laxative use or escalation at the time of CDI testing (accounting for those on chronic laxatives) also decreased across the study period—most dramatically from 2015 vs 2016 (20 vs 14) and 2017 vs 2018 (11 vs 4) (Table 1). Conclusions: At the VASDHS, diagnostic stewardship of C. difficile NAAT with the use of a test-ordering algorithm significantly reduced HO-HCFA CDI incidence and treatment cost. This trend also corresponded with significantly less PPI use at the time of testing and reduced detection of colonization among patients with laxative-induced diarrhea. Diagnostic stewardship may serve as an effective tool to correctly diagnose and treat HO-HCFA CDI, while significantly reducing treatment costs.