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Objective: To model the effects of active detection and isolation (ADI) regarding Clostridioides difficile infection (CDI) in the bone marrow transplant (BMT) unit of our hospital. Setting: ADI was implemented in a 21-patient bone marrow unit. Patients: Patients were bone marrow recipients on this unit. Interventions: We compared active ADI, in which patients who tested positive for colonization of C. difficile before their hospital stay were placed under extra contact precautions, with cases not under ADI. Results: Within the BMT unit, ADI reduced total cases of CDI by 24.5% per year and reduced hospital-acquired cases by ∼84%. The results from our simulations also suggest that ADI can save ∼$67,600 per year in healthcare costs. Conclusions: Institutions with active BMT units should consider implementing ADI.