OBJECTIVES For a recent health technology appraisal in the treatment of chronic idiopathic constipation, direct evidence of the effectiveness of a new intervention (lubiprostone) against the standard of care (prucalopride) was not available. The aim of this study was to review the available data from clinical trials and perform indirect comparisons between the two treatments where possible.  METHODS A literature search (in Medline and other databases) was conducted in December 2013 for trials of lubiprostone or prucalopride. Data for any comparable endpoints were extracted from the papers, and indirect comparisons performed using the Bucher method. RESULTS Four clinical trials for lubiprostone were identified (three company-sponsored, and a small clinician-led trial), as well as three company-sponsored clinical trials for prucalopride. After data extraction, indirect comparisons were possible for seven different endpoints, including the primary efficacy parameter of the lubiprostone studies (Spontaneous Bowel Movements; the relative risk was 1.12 in favour of lubiprostone, 95% CI 0.77-1.64). Other endpoints included the primary efficacy parameter of the prucalopride studies (Spontaneous Complete Bowel Movements), and a range of symptom comparisons. In total, five of the seven indirect comparisons favoured lubiprostone, with statistical significance reached in favour of lubiprostone once and prucalopride once. CONCLUSIONS The indirect comparisons showed that lubiprostone is likely to be at least as effective as prucalopride, with numerical superiority in five out of seven comparisons. However, the number of feasible indirect comparisons on a range of endpoints raises a wider question: which to use in cost-effectiveness modelling? Although analyses generally have a ‘base case’, each of the indirect comparisons adds different information about the relative efficacy of the two products. Given the range of endpoints with associated relative risks, to reduce these to a single comparison (as is current practice) may omit important and relevant information about relative efficacy.