Introduction. Irritable bowel syndrome (IBS) is the most common gastroenterology referral and one of the most common gastrointestinal complaints in primary care. We performed a cost-utility analysis of the most common treatments available in general practice for IBS with constipation (IBS-C), the most expensive IBS subtype. Methods. We developed a decision analytic model evaluating guideline-recommended and Food and Drug Administrationâapproved drugs, supplements, and dietary/psychological interventions. Model inputs were derived from âglobal symptom improvementâ outcomes in systematic reviews of clinical trials. Costs were derived from national datasets. Analysis was performed with a 1-year time horizon from patient and payer perspectives. We analyzed a prototypical managed-care health plan with no cost-sharing to the patient. Results. From a payer perspective, global IBS treatments (including low FODMAP, cognitive behavioral therapy [CBT], neuromodulators), which are not specific to the IBS-C bowel subtype were less expensive than on-label prescription drug treatments. From a patient perspective, on-label prescription drug treatment with linaclotide was the least expensive treatment strategy. Drug prices and costs to manage untreated IBS-C were most important determinants of payer treatment preferences. Effects of treatment on missed work-days and need for repeated appointments to complete treatment were the most important determinants of treatment preference to patients. Discussion. Due mostly to prescription drug prices, neuromodulators, low FODMAP, and CBT appear cost-effective compared to on-label drug treatments from a payer perspective in cost-utility analysis. These findings may explain common treatment barriers in clinical practice.