Patients who have undergone percutaneous coronary intervention (PCI) for coronary artery disease usually get a platelet inhibitor ( clopidogrel) for one year after the procedure. Prasugrel is a new platelet inhibitor which is available for patients with acute coronary syndrome (ACS) who undergo PCI in Norway. We aimed to analyze the efficacy and cost-effectiveness of prasugrel compared to clopidogrel for ACS patients who have undergone PCI. This analysis was commissioned by the Norwegian Medicines Agency to support their decision on whether to give reimbursement to prasugrel as well as clopidogrel, which is reimbursed today. We performed a systematic review of randomised controlled trials (RCTs) to estimate the efficacy of prasugrel compared to clopidogrel. Cost-effectiveness analyses were performed in a previously developed Markov model (MOCCA) which simulates clinical events after a PCI is performed. In the model, health and costs are calculated to give the remaining life expectancy and lifetime costs, which again are used to calculate incremental cost-effectiveness of prasugrel compared to clopidogrel. Prasugrel significantly reduces rates of myocardial infarction and urgent target vessel revascularization compared to clopidogrel in both short term (up to 1 month) and long term (up to 15 months). Quality of the evidence was high and moderate for myocardial infarction and low and moderate for urgent target vessel revascularization. Prasugrel significantly increases rates of bleeding events compared to clopidogrel in both short term and long term data. Quality of the evidence for this outcome was high and low, respectively. The analyses on short and long term effects on mortality revealed no statistically significant differences. Quality of the evidence for this outcome was low and moderate, respectively. Prasugrel is cost-effective compared to clopidogrel for ACS patients who have undergone PCI. Our analyses indicate however that there is uncertainty surrounding the cost-effectiveness result. Uncertainty related to efficacy on mortality and, hence also, cost-effectiveness could be reduced if new randomised controlled trials are performed.