BACKGROUND: Comparative effectiveness research is seen as a powerful tool to assist payers in determining the most effective treatment option when multiple possibilities exist. Whilst head-to-head trials of relevant comparator treatments are uncommon, indirect comparisons, such as Mixed Treatment Comparisons (MTCs), offer the potential to help assess the comparative efficacy of therapies, which can inform payers about their comparative effectiveness. OBJECTIVES: To review the use of MTCs in published technology appraisals from the National Institute for Health and Clinical Excellence (NICE) in the UK. METHODS: All NICE technology appraisals from January 2006 to December 2010 were searched for ‘mixed treatment comparison’. RESULTS: Overall, 17 appraisals containing MTCs were identified. Of these, 24% were for rheumatoid arthritis, 24% for cardiovascular conditions, 18% for cancer and the remainder were for other conditions. In 2010, NICE published 26 appraisals, of which 8 (30.8%) utilised MTCs; in 2009, 26% of appraisals (5/19) incorporated MTCs; in 2008 this figure was 17.4% (4/23) and in 2007 and 2006 no appraisals, out of 19 and 14 published appraisals respectively, contained MTCs. The justification in most cases for the use of the MTCs was to provide an indication of comparative effectiveness for the intervention compared with major competitors and often the findings were incorporated into the manufacturer’s economic model. However, in the majority of appraisals, the Evidence Review Group criticised the design of the MTCs, and in at least 5 cases this led to the Committee either disregarding the results of the MTC or interpreting them with caution. CONCLUSIONS: The value of MTCs for determining comparative effectiveness in Health Technology Assessments cannot be disputed, and they are increasingly becoming a more common feature in the NICE appraisal process. However, manufacturers should ensure that their MTCs are robustly designed otherwise the success of their submission may be jeopardised.