BACKGROUND: The economic burden associated with irritable bowel syndrome with diarrhea (IBS-D) is not well understood. OBJECTIVES: To (a) evaluate total annual all-cause, gastrointestinal (GI) related, and symptom-related (i.e., IBS, diarrhea, abdominal pain) health care resource use and costs among IBS-D patients in a U.S. commercially insured population and (b) estimate incremental all-cause health care costs of IBS-D patients versus matched controls. METHODS: Patients aged >= 18 years with 12 months of continuous medical and pharmacy benefit eligibility in 2013 were identified from the Truven Health MarketScan research database. The study sample included patients with >= 1 medical claim with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code in any position for IBS (ICD-9-CM 564.1x) and either (a) >= 2 claims for diarrhea (ICD-9-CM 787.91, 564.5x) on different service dates in 2013, or (b) >= 1 claim for diarrhea plus >= 1 1 claim for abdominal pain (ICD-9-CM 789.0x) on different service dates in 2013, or (c) >= 1claim for diarrhea plus a 1 pharmacy claim for a symptom-related prescription on different service dates in 2013. Controls included patients with no claims for IBS, diarrhea, abdominal pain, or symptom-related prescriptions in 2013. Controls were randomly selected and matched with IBS-D patients in a 1:1 ratio based on age (+/- 4 years), gender, geographic location, and health plan type. All-cause health care resource utilization included medical and pharmacy claims for health care services associated with any condition. Total health care costs were defined as the sum of health plan-paid and patient-paid direct health care costs from prescriptions and medical services, including inpatient, emergency department (ED), and physician office visits, and other outpatient services. A total cost approach was used to assess all-cause, GI-related, and symptom-related health care costs for IBS-D patients. An incremental cost approach via generalized linear models was used to assess the excess all-cause costs attributable to IBS-D after adjusting for demographics and general and GI comorbidities. RESULTS: Of 39,306 patients (n=19,653 each for IBS-D and matched controls) included, mean (+/- SD) age was 47 (+/- 17) years and 76.5% were female. Compared with controls, IBS-D patients had a significantly higher mean annual number of hospitalizations, ED visits, office visits, and monthly (30-day) prescription fills. Mean annual all-cause health care costs for IBS-D patients were $13,038, with over half (58.4%) attributable to office visits and other outpatient services (e.g., diagnostic tests and laboratory or radiology services), and remaining costs attributable to prescriptions (19.5%), inpatient admissions (13.6%), and ED visits (8.5%). GI-related ($3,817) and symptom related ($1,693) costs were also primarily driven by other outpatient service costs. After adjusting for demographics and comorbidities, incremental annual all-cause costs associated with IBS-D were $2,268 ($9,436 for IBS-D patients vs. $7,169 for matched controls; P < 0.001) per patient/year, of which 78% were from medical costs and 22% were from prescription costs. CONCLUSIONS: IBS-D was associated with a substantial burden in direct costs in this population. Compared with matched controls, IBS-D patients had greater medical service use and incurred significantly more annual all-cause health care costs, even after controlling for demographics and comorbidities. Incremental costs associated with IBS-D were primarily attributable to increased use of medical services rather than pharmacy costs. Copyright (C) 2017, Academy of Managed Care Pharmacy. All rights reserved.