With the advent of reperfusion therapies, management of patients presenting with ST-elevation myocardial infarction (STEMI) has witnessed significant changes during the last decades. We sought to analyze temporal trends in reperfusion modalities and their prognostic impact over a 20-year period in patients presenting with STEMI the Monastir region (Tunisia). Patients from Monastir region presenting for STEMI were included in a 20-year (1998-2017) single center registry. Reperfusion modalities, early and long-term outcomes were studied according to five four-year periods. Out of 1734 patients with STEMI, 1370 (79%) were male and mean age was 60.3 ± 12.7 years. From 1998 to 2017, primary percutaneous coronary intervention (PCI) use significantly increased from 12.5% to 48.3% while fibrinolysis use significantly decreased from 47.6% to 31.7% (p<0.001 for both). Reperfusion delays for either fibrinolysis or primary PCI significantly decreased during the study period. In-hospital mortality significantly decreased from 13.7% during Period 1 (1998-2001) to 5.4% during Period 5 (2014-2017), (p=0.03). Long-term mortality rate (mean follow-up 49.4 ± 30.7 months) significantly decreased from 25.3% to 13% (p<0.001). In multivariate analysis, age, female gender, anemia on-presentation, akinesia/dyskinesia of the infarcted area and use of plain old balloon angioplasty were independent predictors of death at long-term follow-up whereas primary PCI use and preinfaction angina were predictors of long-term survival. In this long-term follow-up study of Tunisian patients presenting for STEMI, reperfusion delays decreased concomitantly to an increase in primary PCI use. In-hospital and long-term mortality rates significantly decreased from 1998 to 2017.