OBJECTIVES The clinical efficacy of lubiprostone in chronic idiopathic constipation has been demonstrated in three randomised clinical trials (RCTs). This analysis assesses the cost effectiveness of lubiprostone compared to prucalopride (the current standard of care), placebo and immediate referral to secondary care from the perspective of the UK National Health Service (NHS). METHODS A state-transition model was constructed to represent the treatment pathway for chronic idiopathic constipation from an NHS perspective with a 1-year time horizon. The model considered treatment continuation rules, at Week 2 for lubiprostone and Week 4 for prucalopride. Clinical data were taken from RCTs and an indirect comparison with prucalopride. Long-term duration of treatment was estimated by fitting curves to open-label study data. Costs included drug costs, medical resource use, and the cost of the pathway including primary and secondary care, obtained from published sources. Quality of life was modelled according to whether constipation was resolved or unresolved, with values taken from a large published study (n=1,200).  RESULTS Compared to placebo, lubiprostone delayed referral to secondary care and improved quality of life, but resulted in increased costs due to treatment, the incremental cost-effectiveness ratio was £2,924. Lubiprostone and prucalopride were found to have similar efficacy, with lubiprostone generating an additional 0.0014 QALYs in the base case. The cost per day for lubiprostone is lower than for prucalopride; leading to lower total costs (£1,596 v £1,655), and meaning lubiprostone dominated prucalopride (lower cost and higher QALYs). Probabilistic sensitivity analysis showed lubiprostone to have an 84% chance of being the most cost-effective treatment at a threshold of £20,000 per QALY. CONCLUSIONS Treatment with lubiprostone provides substantial value to both patients and the NHS, being highly cost effective compared to placebo and dominant compared to the current standard of care.