Background: Coronavirus disease 2019 (COVID-19) pandemic has led to a fast and radical transformation in social, economic, and healthcare networks. COVID-19 outbreak may thus have profound indirect consequences on clinical presentation and management of patients with ST-segment–elevation myocardial infarction (STEMI). Aim of this study was to assess clinical features of patients with STEMI during COVID-19 pandemic. Methods: This single-center, prospective study from a regional public service healthcare hub in Milan included all consecutive patients with STEMI admitted to our institute from February 21 to April 1, 2020 (during COVID-19 pandemic). These patients were compared with a historical cohort of patients admitted for STEMI during the analogous time period (February 21 to April 1) in 2018 and 2019, in terms of time from symptoms onset to hospital admission, clinical characteristics, and in-hospital outcomes. Results: A total of 26 patients were admitted for STEMI during the study period, and 7 (26.9%) of these patients tested positive for severe acute respiratory syndrome coronavirus 2. On admission, medical therapy, including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers use, was similar between cohorts. Median (interquartile range) time from symptoms onset to hospital admission was significantly longer in 2020 as compared to the historical cohort (15.0 [2.0–48.0] versus 2.0 [1.0–3.0] hours; P <0.01). A higher proportion of patients presenting with late presentation STEMI was observed in 2020 compared with the historical cohort (50.0% versus 4.8%; P <0.01). Primary percutaneous coronary intervention resulted indicated in 80.8% of patients in 2020 compared with 100% in the historical cohort ( P =0.06). In-hospital death, thromboembolism, mechanical ventilation, or hemodynamic decompensation needing inotropic or mechanical support were similar between years. Conclusions: These preliminary results from a cardiovascular regional public service healthcare hub demonstrate a significantly longer time from symptoms onset to hospital admission among patients with STEMI during COVID-19 pandemic compared with the same time period in the previous 2 years.