- The aim of this study was to assess age differences in the utilization of class-I treatment guidelines and its effect on mortality in patients with ST-elevation myocardial infarction (STEMI). The study included 1026 consecutive patients from the prospective nationwide Acute Coronary Syndrome Israeli Survey (ACSIS). Primary reperfusion was used less often among elderly (age > 75 years) patients than among those aged 65–74 and <65 years (46%, 63%, 64%, respectively, p (for trend) = 0.004). Class-I evidence-based medications (EBM) at discharge (aspirin, β-blockers, angiotensin converting-enzyme inhibitors = ACEI, angiotensin receptor-blockers = ARBs and statins) were less frequently prescribed to elderly compared to younger age-subgroup (44%, 61%, 57%, respectively; adjusted odds ratio (OR) = 0.62; 0.40–0.97 for age ≥ 75 vs. age < 65 years). Early and 1-year mortality rates were 3–5-fold higher among the elderly compared to patients <65 years. In the entire cohort use of primary reperfusion was associated with lower 1-year mortality (OR = 0.69; 0.47–1.01), as was the use of EBM (OR = 0.26; 0.17–0.41). These effects were similar across all age-subgroups but with a greater impact among the elderly, as the number of patients needed to treat (NNT) was significantly lower with advancing age. Better adherence to treatment guidelines may improve the prognosis of elderly patients with STEMI.