The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer (The Medicines Company) of bivalirudin to submit evidence for its clinical and cost effectiveness within its licensed indication for the treatment of adults with ST-segment elevation myocardial infarction (STEMI) intended for primary percutaneous coronary intervention (PPCI), as part of NICE’s single technology appraisal (STA) process. The School of Health and Related Research (ScHARR) at the University of Sheffield was commissioned to act as the Evidence Review Group (ERG), which produced a review of the evidence within the manufacturer’s submission to NICE. This article describes the manufacturer’s submission, the ERG review and NICE’s subsequent decisions. The main evidence was derived from one randomized controlled trial (RCT) of STEMI patients intended for PPCI, comparing bivalirudin with unfractionated heparin plus glycoprotein IIb/IIIa inhibitors (GPIs). Bivalirudin was associated with a significant reduction in cardiac mortality at 30 days (p = 0.03) and at 1-year follow-up (p = 0.005), and a significant reduction in major bleeding at 30 days (p < 0.001) and 1 year (p < 0.0001), compared with heparin plus GPI. Stent thrombosis up to 24 hours following PPCI was significantly (p < 0.001) more common with bivalirudin. However, there was no significant treatment effect for stent thrombosis from 1 to 30 days (p = 0.28), or at 1-year follow-up (p = 0.53). There were no significant treatment group differences at 30 days and at 1 year in stroke (p = 0.68 and p = 0.99, respectively), in myocardial infarction [MI] (p = 0.90 and p = 0.22, respectively), or in the need for the revascularization of the target vessel for ischaemia (p = 0.18 and p = 0.12, respectively). There were two decision-analytic models: the base-case scenario used 1-year follow-up data from the RCT; and a sensitivity analysis used 3-year follow-up data. Resource use was primarily drawn from this RCT. Health-related quality-of-life (HR-QOL) estimates were drawn from a UK cohort study. Both models evaluated the incremental costs and outcomes of bivalirudin compared with heparin plus GPI for patients with STEMI intended for PPCI. The analysis adopted a UK NHS perspective over a lifetime horizon. Unit costs were based on year 2009–2010 prices. The model adopted a decision-tree structure to reflect initial events for the initial period (stroke, repeat MI, minor/major bleeding events, repeat revascularization and death) and a two-state Markov component to simulate longer-term survival. The economic analysis suggested that bivalirudin is expected to dominate the heparin plus GPI strategy. This finding was consistent across the probabilistic sensitivity analysis and the vast majority of deterministic sensitivity analyses undertaken. Three exceptions to this finding were observed for the following sensitivity analyses: (1) the exclusive use of eptifibatide as the GPI (incremental cost-effectiveness ratio [ICER] = £1,764); (2) the combination of 100 % eptifibatide use, 100 % radial arterial access and no differential length between strategies for initial hospital stay (ICER = £4,106); and (3) a longer length of ward stay (increase of 0.33 days) for the initial hospitalization (ICER = £415). The Appraisal Committee (AC) gave a positive recommendation for bivalirudin for the treatment of adults with STEMI undergoing PPCI.