To examine the extent to which evidence-based beneficial therapy is applied in practice, whether this is changing over time and is associated with improved outcomes. Randomized trials have proved efficacy of several treatments for acute myocardial infarction (AMI) with ST-elevation (STEMI), non-ST-elevation (NSTEMI) and bundle branch block (BBB). We prospectively examined all 6748 consecutive patients with AMI aged 25-74 years hospitalized in the study region's major clinic stratified into four time-periods: 1985-1989 (n = 1622), 1990-1994 (n = 1588), 1995-1999 (n = 1450) and 2000-2004 (n = 2088). The increase in numbers of AMI in the last period was mainly, but not exclusively driven by NSTEMI cases. Evidence-based pharmacological therapy increased steeply over time. Invasive procedures increased mainly in the last period with percutaneous coronary intervention and coronary artery bypass graft performed in 30% and 15% in 1998 and 66.0% and 22%, respectively, in 2004. In-hospital complications and 28-day-case fatality decreased significantly from period 1 to period 4 in all patients with AMI. Marked reductions in 28-day-case fatality were mostly seen in BBB patients during the last period (25.3% vs. 10.3%, P < 0.001). Of interest, the odds in 28-day-case fatality reduction was diminished after correction for recanalization therapy (from 0.35, 95% CI: 0.16-0.74 to 0.52, 95% CI: 0.19-1.45). Over the past 20 years, there were substantial changes in pharmacological and interventional therapies in AMI accompanied by reductions in in-hospital complications and 28-day-case fatality in all infarction types with marked reductions in 28-day-case fatality in BBB patients. The latter observation may mainly be because of the increased use of interventional therapy.