Clostridium difficile infection (CDI) has become the leading cause of healthcare associated infections in the United States and currently accounts for 15% to 20% of infectious diarrhea in the healthcare setting.  Accurate diagnosis of CDI is criticalin promoting effective management of patients and implementing appropriate infection control measures to disrupt and prevent transmission.  Reliable diagnostic tests are needed to confirm or negative a presumptive clinical diagnosis of CDI.  Nucleic acid amplification tests (NAAT) have become available within the last ten years and have been used in one of two ways: 1) Direct testing, 2) algorithmic testing as a supplement to enzyme immunoassay (EIA) for the detection of glutamate dehydrogenase and Toxin A/B.  Much controversy exists as to which approach, direct NAAT or algorimthic is optimal for the laboratory diagnosis of CDI.  The latest NAAT-based test to enter the market is the Simplexa C. diffcile Direct Assay,   An evaluation of this technology was conducted for the purpose of determining its overall performance and potential integration into two-step algorithm testing format.  The assay was evaluated and compared to two other NAAT platforms.  The results of this evaluation are the subject of this presentation.