OBJECTIVES: Head-to-head randomized controlled trials (RCTs) remain the gold standard for establishing relative treatment efficacy and for use in cost-effectiveness (CE) models. However, in some cases, such as rare diseases, only single-arm trials may be available. We identified health technology appraisals (HTAs) published by the National Institute for Health and Care Excellence (NICE) that included evidence from single-arm trials and reviewed the use of the single-arm trial data in accompanying CE models.  METHODS: We searched the NICE website for published technology appraisals using the term “single-arm”. We reviewed HTAs in which single-arm trials were used and recorded the date of the appraisal, disease area, use of the single-arm trial data, the NICE recommendation, and NICE’s comments on the use of the single-arm trials.  RESULTS: Twenty-two HTAs included a reference to one or more single-arm trials. Fourteen provided the single-arm trial data only as supporting evidence to at least one RCT. Of the eight that used single-arm trial data, all also used the data in a model; four used the data as the primary evidence of efficacy, two used the data to extend an RCT, and two used the data for other inputs. Only one of the four using the data for evidence of efficacy resulted in a positive recommendation from NICE. In this case, evidence was from seven single arm trials; two manufacturer models and the assessment group model all demonstrated the intervention to be dominant over standard care, and several other factors may have contributed to a positive recommendation. In the three HTAs resulting in a negative recommendation, NICE expressed concerns over the efficacy data.  CONCLUSIONS: Although RCTs are preferred for relative efficacy data for use in cost-effectiveness analyses in NICE HTAs, there is one case of a positive NICE recommendation despite efficacy evidence being based on single-arm trials.