During the coronavirus pandemic 2019 (COVID-19), some studies showed differences in the profile of subjects presenting with acute coronary syndromes as well as in overall mortality due to the delay of presentation and other complications. The purpose of this study was to compare the profile and outcomes, with emphasis on all-cause in-hospital mortality, of ST-elevation myocardial infarction (STEMI) subjects presenting to the emergency department during the pandemic period compared with a control group from the previous year, 2019. The study enrolled 2011 STEMI cases, which were divided into two groups—pre-pandemic (2019–2020) and pandemic period (2020–2022). Hospital admissions for a STEMI diagnosis sharply decreased during the COVID-19 period by 30.26% during the first year and 25.4% in the second year. This trend was paralleled by a significant increase in all-cause in-hospital mortality: 11.5% in the pandemic period versus 8.1% in the previous year. There was a significant association between SARS-CoV-2 positivity and all-cause in-hospital mortality, but no correlation was found between COVID-19 diagnosis and the type of revascularization. However, the profile of subjects presenting with STEMI did not change over time during the pandemic; their demographic and comorbid characteristics remained similar.