OBJECTIVES: The National Institute for Health and Care Excellence (NICE) established the Single Technology Appraisal (STA) programme to evaluate the clinical and cost-effectiveness of medical technologies and provide mandatory guidance on how they should be used within the National Health Service (NHS) in the UK. The objective of this analysis is to explore how NICE advice differs between preliminary and final guidance in the STA process and identify actions manufacturers could take to increase their chances of a successful submission. METHODS: For STAs published between February 2010 and May 2013, the appraisal consultation document (ACD) and final appraisal determination (FAD) were identified. The guidance issued in these documents was compared and contrasted, and the key clinical and economic evidence that affected recommendations were extracted into an Excel workbook. RESULTS: Of the 71 STAs published, ACDs were produced for 60 technologies, while 11 (15%) proceeded straight to FAD. All submissions which proceeded directly to FAD were recommended (full or optimised) in the final guidance. Twelve STAs (20%) received a “minded no” at ACD; however, 11 of these (92%) were reversed within the FAD on the basis of additional data provided by the manufacturers in the form of economic analyses (n=5) or patient access schemes (PAS) (n=6). Of the 35 “not recommended” at ACD, 15 (43%) were ultimately recommended within the FAD through the introduction or revision of a PAS and/or submission of additional analyses. CONCLUSIONS: If manufacturers can demonstrate a robust clinical and economic argument in their initial submission the chances of a FAD being produced without the requirement of an ACD are greatly increased. Furthermore, ACD decisions can also be overturned; technologies which receive a “minded no” or “not recommended” at ACD stage can achieve a recommendation at FAD by presenting additional analyses or introducing/modifying a PAS.