Background: Acute coronary syndrome (ACS) is a condition of acute and critical myocardial ischemia. It is most often manifested as unstable angina pectoris and myocardial infarction. It is a syndrome that is considered among the greatest emergencies in cardiology and medicine in general. The impact of the SARS-CoV-2 virus on the heart is multifaceted, from the development of possible myocarditis, the formation of thrombosis in small blood vessels and consequent necrosis, but also the occurrence of type 2 myocardial infarction and the development of classic ACS, type 1 myocardial infarction. For optimal treatment of these patients an adequate understanding of the interaction between COVID-19 and cardiovascular diseases is needed. Aim: To examine the characteristics of acute coronary syndrome patients hospitalized at the Institute for Heart and Blood Vessel Diseases at the Sveti Duh Clinical Hospital before and during the COVID-19 pandemic. Methods: A retrospective study compared two groups of patients with ACS in the period from January to December 2018 and January to December 2020. Results: The data of 729 patients were analyzed. The most common risks present in patients are diabetes and smoking, with no significant difference compared to the observed age. Hypertension is more frequent in 2020, and dyslipidemia is more significant in 2018. Patients hospitalized in 2020 have a significantly higher body mass, as well as a higher body mass index, compared to 2018. With regard to the diagnosis, in 2020 ST-elevation myocardial infarction (STEMI) and unstable angina pectoris (NAP) are significantly more frequent, and in 2018 non-ST-elevation myocardial infarction (NSTEMI). The number of days of hospitalization was significantly longer in 2018 (median 5 days) compared to 2020 (4 days). Conclusion: During the pandemic year 2020, not a single hospitalized patient with ACS had previously recovered from COVID. Only two patients had ACS in addition to the COVID-19 infection. There was no significant difference in the number of hospitalizations or in the structure of patients in the investigated periods. During the pandemic, there were more patients with hypertension and higher body mass, and fewer with dyslipidemia.