Background Prasugrel is a potent thienopyridine that may be preferentially used in younger patients with lower bleeding risk. Objective We compared prasugrel use and outcomes by age from the PROMETHEUS study. We also assessed age-related trends in treatment effects with prasugrel versus clopidogrel. Methods PROMETHEUS was a multicenter acute coronary syndrome (ACS) percutaneous coronary intervention (PCI) registry. We compared patients in age tertiles (T1 < 60 years, T2 60-70 years, T3 > 70 years). Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke or unplanned revascularization. Data were adjusted using multivariable Cox regression for age-related risks and propensity score stratification for thienopyridine effects. Results The study included 19,914 patients: 7045 (35.0%) in T1, 6489 (33.0%) in T2 and 6380 (32.0%) in T3. Prasugrel use decreased from T1 to T3 (29.2% vs. 23.5% vs. 7.5%, p < 0.001). Crude 1-year MACE rates were highest in T3 (17.4% vs. 16.8% vs. 22.7%, p < 0.001), but adjusted risk was similar between the groups (p-trend 0.52). Conversely, crude incidence (2.8% vs. 3.8% vs. 6.9%, p < 0.001) and adjusted bleeding risk were highest in T3 (HR 1.24, 95% CI 0.99-1.55 in T2; HR 1.83, 95% CI 1.46-2.30 in T3; p-trend < 0.001; reference = T1). Treatment effects with prasugrel versus clopidogrel did not demonstrate age-related trends for MACE (p-trend = 0.91) or bleeding (p-trend = 0.28). Conclusions Age is a strong determinant of clinical risk as well as prasugrel prescription in ACS PCI with much lower use among older patients. Prasugrel did not have a differential treatment effect by age for MACE or bleeding. Graphic abstract Frequency of prasugrel use and age-related temporal risks of all-cause death and bleeding after ACS PCI.