OBJECTIVES: Linaclotide is the first drug that received EMA approval in the management of irritable bowel syndrome in its constipation form (IBS-C). We aimed at estimating the cost-utility of linaclotide, compared to standard of care (SoC) in Belgium. METHODS: The analysis was conducted using data from a 6-month randomized trial of linaclotide 290µg once daily (N=401) versus placebo (N=403), which provided monthly EQ-5D measures, treatment duration, adverse events (diarrhoea) and responder status (abdominal pain/discomfort improvement ≥ 30% from baseline). Belgian EQ-5D tariffs were used to estimate utilities and trapezoidal rule to estimate QALYs. A Delphi panel including 6 general practitioners and 5 gastro-enterologists provided the resource use for IBS-C patients in different treatment phases: controlled with 2nd line or new drug else non-responders. Patient-level costs were applied using first-order Monte-Carlo simulation (gamma distribution function; per treatment arm and responder status; health care payer perspective). A stopping rule was implemented at 4 weeks for linaclotide non-responders. A non-parametric bootstrap with 1000 replications was performed. The 2012 Belgian GDP per capita (€34,000) was used as willingness-to-pay threshold. RESULTS: The responder rate at 4 weeks was 54.6% with linaclotide vs. 35.5% with SoC. There was on average 0.0129 QALYs gained per linaclotide patient vs SoC at 6 months (0.385 vs. 0.372), with an incremental cost of €95 (€1,376 vs. €1,280). The incremental cost-effectiveness ratio of was €7,364/QALY. The diarrhoea costs were higher with linaclotide (+€19.4) while savings were observed in clinical management (-€132.2) compared to SoC. Using a willingness-to-pay threshold of €34,000/QALY, 66% of the simulations were cost-effective. CONCLUSIONS: Due to improvements in abdominal pain/discomfort complaints in patients receiving linaclotide, savings were generated in the clinical management of IBS-C compared to SoC. Using the GDP per capita as willingness-to-pay threshold, linaclotide seems a cost-effective alternative to today SoC of IBS-C in Belgium.