Objective: Stakeholder involvement in health technology assessment (HTA) is of growing importance, as their participation in and support of economic evaluation is generally considered to improve the assessment process and subsequent implementation. Consequently, in early 2007, the Health Select Committee of the UK House of Commons initiated a public inquiry into the National Institute of Health and Clinical Excellence (NICE), calling for comments from a variety of stakeholders. This study aimed to examine stakeholder perspectives on several topics, including public confidence in NICE; appropriateness of economic evaluation methods; and, effectiveness of guidance implementation. Methods: All stakeholder submissions (n=92) were systematically reviewed and key themes were identified across three principal categories: 1) organisation and process, 2) methods, and 3) decision-making and implementation. Results: Stakeholders identified a number of overarching issues regarding NICE and economic evaluation, more broadly. Firstly, despite its “arms-length” organisational structure, NICE is perceived to lack independence. Secondly, stakeholders contented that its methods assume an overly narrow perspective, especially regarding the use of RCTs, QALYs, and measures of costs and benefits. Thirdly, commentators asserted that manufacturers, clinical experts, and patients should play a greater role in HTA processes. Fourthly, the time taken to issue guidance was considered an important limitation, especially given evidence that local decision-makers delay the introduction of new treatments pending NICE's decision(s). Other key concerns included inconsistent local implementation of guidance and the overall transparency of NICE operations. Conclusion: Most stakeholders support the overall role of NICE in the NHS, and acknowledge that the Institute generally undertakes rigorous assessments. Nevertheless, many criticisms were put forth by stakeholders. NICE should continue to capitalise on its strengths, while pioneering solutions to address existing limitations and challenges. However, it is unlikely that any national HTA system will satisfy the needs and expectations of all key parties.