Introduction <p>Restrictions of cross-border mobility were used during the COVID-19 pandemic to slow down transmission between countries. Such restrictions came with significant societal costs, and their effect on in-country burdens of COVID-19 has been questioned. Our study aims to assess whether cross-border transmission contributed significantly to in-country burdens of COVID-19 in four large Euroregions shared by the Netherlands, Germany and Belgium.</p> Method <p>Geographical information systems (GIS) and Besag-York-Mollie (BYM) models were used to visualize the spatial distribution of COVID-19 cases from January 2020 through October 2022. Space-time cluster analysis with SaTScan was used to identify significant clusters of COVID-19 cases and determine whether they included cross-border areas. Over 4 million cases drawn from the national infectious disease registries were analysed for this study.</p> Results <p>Incidence of COVID-19 increased and decreased independently within each country, except for one simultaneous peak in January 2022 due to the Omicron variant. Eight significant space-time clusters were identified, four of which were cross-border clusters. All eight clusters occurred during periods of high in-country transmission.</p> Discussion <p>Our findings showed that cross-border transmission did not contribute in significant ways to in-country burdens of COVID-19 burden in the regions studied. The identified clusters corresponded to in-country waves of infection. Our results challenge the assumption that border closures were crucial in controlling the pandemic and highlight the need for coordinated public health responses that balance the effect of interventions with societal costs.</p>