OBJECTIVES: In patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI), the TRITON-TIMI 38 trial demonstrated that treatment with prasugrel vs. clopidogrel was associated with significantly reduced rates of atherothrombotic events, though with increased risk of bleeding.  We evaluated the long-term cost-effectiveness of a 12-month treatment with prasugrel vs. clopidogrel in the trial population, excluding patients with prior transient ischemic attack or stroke, from the perspective of the German health care system. METHODS: A Markov model was developed based on risk equations for cardiovascular death, myocardial infarction (MI) or stroke, bleeding, and rehospitalisation, derived from TRITON-TIMI 38 data (N=13,608 patients). Hospital readmissions captured during the trial in all patients from 8 countries (N=6705) were assigned to German diagnosis related groups, and hospitalisation costs continued to accrue beyond 12 months to all surviving patients. Long term survival and quality adjusted survival were estimated for the life-time of each patient. RESULTS: At 12 months, a difference in drug costs between prasugrel and clopidogrel of +105 (branded clopidogrel) to +€416 (generic clopidogrel) per patient was partially or totally offset by hospital cost savings (-€129 per patient) due principally to reduced rates of revascularization. In the longer-term, prasugrel was associated with higher total costs (+€42 to +€353 per patient), life expectancy gains of 0.07 years, due primarily to the reduced rate of MI, and 0.05 additional QALYs, resulting in incremental costs per life year saved and per QALY gained of €606 to €5074 and €799 to €6689, respectively. Probabilistic sensitivity analysis indicated that prasugrel has a ≥79 to 88% probability of being more cost-effective than clopidogrel at a willingness to pay of €30,000 per QALY. CONCLUSIONS: Prasugrel given for up to 1 year in ACS-PCI patients is likely to be considered a highly cost-effective treatment strategy.