OBJECTIVES: Indirect and Mixed Treatment Comparisons (ITC/MTC) can provide valuable information for decision-makers, especially when direct comparisons between medicines are unavailable. The objective of this study is to investigate the methods and impact of ITC and MTC submitted by manufacturers on the NICE committee’s appraisal of pharmaceuticals. METHODS: A search of the NICE website was conducted for manufacturers’ submissions that reported to contain either an ITC or MTC since 2006.  Data were extracted and analysed for the type of network meta-analysis, number of trials, head-to-head trial evidence available, disease area, treatment comparisons, study selection justification, sensitivity analysis of trial selection and outcome(s). The impact was assessed by analysing information on Evidence Review Group (ERG) review of evidence synthesis, Appraisal committee’s comments and final decision. RESULTS: The search identified 24 submissions that included either a MTC or ITC. The issues most frequently raised by the ERG were lack of reporting of trial characteristics, description of methods and quality assessment of all trials included. The most frequent validity concerns were both clinical and statistical heterogeneity between trials, inappropriate methods of analysis, exclusion of relevant trials and sparse numbers of trials in the network. The committee considered all evidence and reported the analysis to be plausible on one occasion, stated concerns with the validity in 18 appraisals and did not directly comment on 5 occasions. Fifty eight percent of appraisals including an MTC or ITC resulted in a restricted decision. CONCLUSIONS: ITC and MTC analysis has provided additional useful information for NICE appraisals but there has been wide variation in the reporting and validity of analysis performed. Reimbursement agencies should establish guidelines for the conduct of ITC and MTC to reduce this variation. The emerging ISPOR Good Research Practice guide on indirect treatment comparisons will provide a basis for these.