OBJECTIVES: While non-US agencies such as NICE (National Institute for Health and Clinical Excellence) in the UK have been conducting Health Technology Assessments (HTAs) for over ten years, Comparative Effectiveness Research (CER) as conducted in the US is relatively recent. The lack of economic considerations is one well-defined distinction between CER and HTA. The aim of this research is to compare CER publications from AHRQ (Agency for Healthcare Research and Quality) with HTA-related publications from NICE to determine whether there are other consistent, clear distinctions of note. METHODS: All 22 AHRQ CER publications published on the National Institutes of Health website were assessed. Conclusions relating to the comparative effectiveness of pharmaceuticals on major clinical outcomes were compiled. The NICE website was searched for corresponding HTA guidance, and conclusions and other features of the publications were compared. RESULTS: Of the 14 AHRQ CER publications that assessed pharmaceuticals, for only two of these were there corresponding NICE HTAs. The CER publication on Rheumatoid Arthritis and Psoriatic Arthritis corresponded to two NICE HTAs, which were both in general agreement with the CER report. In contrast, the conclusion from the CER publication on Lipid-Modifying Agents stated that there was insufficient clinical evidence to guide decisions, whereas NICE was confident enough in the evidence to make a subsequent access decision. In its Clinical Guideline (CG) documents NICE also provided statements relevant to three other AHRQ CER report topics; all were in general agreement with the AHRQ CER conclusions. The most notable distinctions between CER and HTA reports, however, were in their scope, breadth, and purpose. CONCLUSIONS: Where like-for-like comparisons were possible, this research found more agreement than disagreement between AHRQ and NICE. The major distinctions of note related to the topics chosen for assessment by the two agencies, which reflect differences in priorities between health systems.