OBJECTIVES: IBS-D/M is typically diagnosed via clinical presentation and testing that excludes other conditions. A novel second-generation blood test quantifies anti-vinculin and anti-CdtB biomarkers to rule-in a diagnosis of IBS-D/M. This study seeks to estimate the economic impact associated with the second-generation blood test compared to the standard exclusionary approach for diagnosing IBS-D/M. METHODS: A cost-minimization decision tree was constructed in TreeAge Pro 2019. Six gastroenterology providers were surveyed to understand the typical diagnostic framework for IBS-D/M, including utilization probabilities of tests and procedures and the probability of treatment as a function of test results. For the second-generation blood test arm, sensitivity, specificity, and likelihood ratios determined how patients advanced to treatment. Patients negative for the second-generation blood test subsequently moved down the standard exclusionary arm. Input costs were drawn from the 2019 MDsave weighted national average. Probabilistic sensitivity analysis (PSA) was performed to determine 95% confidence intervals for costs. Decision tree results informed a budget impact model with 1M covered lives. RESULTS: Survey results indicated 15 tests or procedures that may be used to exclude other conditions when diagnosing IBS-D/M. The decision tree model revealed a mean diagnostic cost per patient of $1129 for the second-generation blood test arm compared to $2049 for the standard exclusionary arm. The PSA produced 95% confidence intervals for cost of $997 - $1275 for the second-generation blood test arm and $1528 - $2443 for the standard exclusionary arm. The budget impact model determined savings of $0.52 per-member-per-month when 50% of patients with possible IBS-D/M take the second-generation blood test. CONCLUSIONS: This model demonstrates potential savings of $253 - $1446 per patient for the second-generation blood test compared to exclusionary diagnosis of IBS-D/M by reducing the need for expensive diagnostic procedures, with annual aggregate plan savings of $6.2M possible when 50% of potential IBS-D/M patients utilize the second-generation blood test.