Abstract Background Guidelines recommend ticagrelor over clopidogrel in patients with AMI, irrespective of their age. The PLATO trial, which showed lower mortality with ticagrelor, included only few very elderly patients. Purpose To analyze one- and 5-year outcomes according to use of ticagrelor vs clopidogrel as first P2Y12-inhibitor at the acute stage of AMI, in real-life conditions in patients aged ≥80 years. Methods FAST-MI 2015 included consecutive patients with AMI in 204 centers throughout France. This analysis focused on patients ≥ 80 years of age, in whom the first P2Y12-inhibitor used was either clopidogrel or ticagrelor. Both Cox time-dependent logistic regression and propensity score (PS) matching were used. Results Among 5,291 patients, 995 (19%) were aged ≥ 80 years, of whom 721 (72%) met the inclusion criteria. Mean age was 86 ± 4 years for patients receiving clopidogrel and 84±3 for those receiving ticagrelor, 54% and 52% respectively were women, and 37% vs 54% had STEMI. Using Cox time-dependent regression, the HR (95%CI) for use of ticagrelor vs clopidogrel first was 1.11 (0.75-1.67), P=0.59 for one-year death and 0.61 (0.43-0.86), P=0.004 for death from one to 5 years. After PS matching, the two cohorts (N=231 each) were well balanced; one-year mortality was similar for the 2 medications, while 5-year survival was higher for those receiving ticagrelor first (Figure). Conclusion In this real-world population of elderly patients (mean age 85 years) with AMI, the use of ticagrelor as the first P2Y12-inhibitor was associated with similar survival at one year and improved survival at 5 years, compared with clopidogrel. The diverging one- and 5-year results suggest the possibility of unmeasured confounders. Further research is needed in older patients.Kaplan-Meir curves: survival at 5-years