We evaluated the analytical and workflow characteristics of the ARIES Clostridium difficile assay, a recently developed qPCR-based test for toxigenic C. difficile. ARIES was compared to the illumigene C. difficile assay, a commonly employed, loop-mediated amplification technique with similar sample-to-result capabilities. Following illumigene analysis, 122 positive and 164 negative stool specimens were banked for subsequent ARIES testing. The analytical agreement between the platforms was high: 93.4% positive agreement (89.0–97.8%) and 97.5% negative agreement (95.2–99.9%). For discordant specimens, amplification/bidirectional sequencing of tcdA/tcdB demonstrated toxigenic C. difficile in 2/4 illumigene(−)ARIES(+) and 2/8 illumigene(+)ARIES(−) specimens. In a time-motion study, the ARIES assay required less hands-on time than illumigene, but with greater total testing time. Overall, these findings support the ARIES C. difficile Assay as a new option for laboratories in their diagnostic repertoire.