Pandemics, including Covid-19, highlight the issue of multilevel governance, where and how powers should be allocated, and the challenge of ensuring coherency. This issue comes clearly into focus in epidemiological units where internal jurisdictional boundaries exist, as in the case of the island of Ireland with the border between Northern Ireland/the United Kingdom and Ireland. This paper evaluates the approaches to policy-making on the island of Ireland, and considers whether the two jurisdictions adequately addressed cross-border issues in light of the concept of subsidiarity. The core focus is on the Memorandum of Understanding (MOU) ‘Covid-19 Response – Public Health Cooperation On An All-Ireland Basis’ agreed between Ireland and Northern Ireland in April 2020, with consideration also given to the alternative proposals for a two-island approach. The paper argues that subsidiarity would call for a centralised approach or at least substantial cooperation to facilitate effective policy implementation and coherency. The MOU reflects these ideas, through supporting substantial cooperation, but with some significant weaknesses that manifest in its implementation. Alternative issues arise when considering a potential two-island approach. Together, the MOU and the alternative of a two-island approach highlight that context is a crucial consideration for subsidiarity and evaluating the approaches to cross-border issues – it can make centralisation and substantial cooperation (and therefore coherency more generally) significantly more challenging and thereby also highlights the limits of subsidiarity.