Abstract Background Throughout the COVID-19 pandemic many countries reported a decline in myocardial infarction (MI) and stroke admissions. Factors leading to the decline remain uncertain. Purpose In this nationwide study spanning the first two years of the COVID-19 pandemic we evaluated the changes in MI and stroke admissions as the effect of pandemic intensity and nationwide lockdown. We also investigated sex and age differences. We benefited from the fact that the Czech Republic had both, the lowest and one of the highest COVID-19 incidence. Methods We compared the first (March 1, 2020, to February 28, 2021) and the second (March 1, 2021, to February 28, 2022) pandemic years overall and during the COVID-19 waves with the preceding year (March 1, 2019, to February 28, 2020). The occurrence of MI and stroke, patient characteristics, and mortality data were obtained from two nationwide registers covering every hospitalization and every death in the Czech Republic. Results During the first and second pandemic year as compared to the preceding year there were 13,856 and 14,123 vs 15,499 MI admissions, representing a -10,6% (p<0.001) and -8,9% (p<0.001) decline; and 23,194 and 23,231 vs 25,046 stroke admissions, representing a -7.4% (p<0.001) and -7.2% (p<0.001) decline respectively. The significant decline appeared in both MI and stroke in all COVID-19 waves (spring 2020, spring 2021, autumn 2020/winter 2021, -autumn 2021/winter 2022). The greatest MI hospitalization decline (-16%) occurred during the first strict national lock down, during the first COVID-19 wave (spring 2020), the pandemic wave with the lowest COVID-19 incidence. Both, MI and stroke admissions reversed to pre-pandemic numbers during the summer (2020, 2021) when most lockdown restrictions were lifted. The decline in MI was greater in women than in men during both the first (-11.8%, -10%; p<0.001) and second (-10.8%, -7.9%; p<0.001) pandemic years, also for stroke in women greater than in men during the first (-9%, -5.9%; p<0.001) and second (-9.7%, -4.8%; p<0.001) pandemic years. The 30-day all-cause mortality in patients with MI was higher during the first (10.6%; p<0.001) but not the second (9.6%; p=0.34) pandemic year as compared to the preceding year (9.3%), whereas the 30-day mortality in patients with stroke remained unchanged. Conclusions There was a decline in both MI and stroke admissions during the first two years of the pandemic, but such decline was not related to COVID-19 incidence. The greatest reduction in both, MI and stroke admissions, appeared during the first lockdown in the first COVID-19 wave (spring 2020), the period of the lowest COVID-19 incidence. Moreover, the decline in MI and stroke admissions was greater in women. This highlights potential sex differences in health effect. Health authorities should be aware of these findings, in order to adapt their message and restriction measures in case of future major epidemics.Myocardial infarction casesStroke cases