The aim of our study was to compare the outcome of patients with a first acute myocardial infarction (AMI) among three large cohorts of patients hospitalized between 1966 and 1992 in Israel, in view of changes in treatment facilities and investigation methods. Patients with a first AMI constituted 71% of all myocardial infarctions in 1966, 74% in 1981-1983, and 71% in 1992. The male-female ratio and the distribution of the site of infarction also remained stable from 1966 to 1992. The mean age of patients increased over time. Thrombolytic therapy was not available in 1966 and 1981-1983, whereas 53% of patients were treated with a thrombolytic agent and 22% examined with coronary angiography in 1992. The 21-day mortality rate decreased markedly, from 22% in 1966 to 14% in 1981-1983 and to 8% in 1992. The decrease was similar in both genders and among 10-year age groups. The 1-year postdischarge mortality rate (not evaluated in 1966) decreased from 7% in 1981-1983 to 6% in 1992. We conclude that a significant reduction in mortality rate after a first AMI took place over the 25-year period. Changes in treatment modality and management of the acute phase may explain this decrease in mortality rate over time.