This study aimed to assess the cost utility of orlistat treatment based on (i) criteria from recent guidance from the National Institute for Clinical Excellence (NICE) for England and Wales (treatment discontinued if weight loss < 5% at 3 months; and < 10% at 6 months); and (ii) alternative criteria from the European Agency for the Evaluation of Medicinal Products (EMEA) licence for orlistat prescription in the European Community (treatment discontinued if weight loss < 5% at 3 months). Subjects were 1398 obese individuals who participated in three large European Phase III trials of orlistat treatment for adults (BMI: 28–47 kg m−2). Measures were: response to treatment in orlistat and placebo treatment groups; health benefit expressed as quality adjusted life years (QALYs) gained associated with weight loss; costs associated with orlistat treatment. In the cost utility model with multiway sensitivity analysis, the cost/QALY gained using the NICE criteria was estimated to be £24 431 (sensitivity analysis range: £10 856 to £77 197). The cost/QALY gained using the alternative EMEA criteria was estimated to be £19 005 (range: £8840 to £57 798). In conclusion, NICE guidance for the continued use of orlistat was supported in this updated cost utility model, comparing favourably with a previously published estimate of £45 881 per QALY gained. Moreover, the value for money of orlistat treatment is improved further if EMEA treatment criteria for continued orlistat treatment are applied. The EMEA criteria should be considered in any future changes to the NICE guidance or in guidance issued by similar agencies.