Aims. Studies on the incidence, acute and subsequent mortality from myocardial infarction are limited mostly to selected clinical cohorts and populations and cover relatively short periods. Our aim was to describe and analyse long-term trends on a national scale. Methods. Acute myocardial infarction (AMI) was defined by the International Classification of Diseases (ICD)10; codes I21 and I22. Our natiowide 1994-2016 data on AMI mortality were obtained from the official mortality statistics (Czech Bureau of Statistics), data on morbidity (hospitalizations) from the National Register of Hospitalizations (Institute for Health Information and Statistics). For further analyses, data from the Czech EUROASPIRE I-V and Czech IMPACT studies were used. Results. Over the 1994-2016 period the total number of AMI cases per year decreased from 34,084 to 19,015, that of patients hospitalized for AMI from 22,373 to 15,419, the total number of deaths due to AMI from 14,834 to 4,673, in those treated because of AMI from 3,794 to 1,137, and hospital fatality in patients treated for AMI decreased from 17% to 7.5%. Over the years 1997-2016, the one-year all-cause mortality rate after AMI declined from 25.1 to 17.9%, cardiovascular (CV) mortality from 22.3 to 14.2%, five-year all-cause mortality from 41.7 to 34%, and CV mortality from 34.1 to 23.6%. Conclusion. The Czech Republic has witnessed a pronounced decrease in AMI incidence and fatality and, consequently, long-term mortality. The decreasing incidence and improving course of AMI are due to progress in primary prevention, in acute coronary care and interventional cardiology, and in secondary coronary heart disease (CHD) prevention.