Nanoparticles represent an attractive option for systemic delivery of therapeutic compounds to the heart following myocardial infarction. However, it is well known that physicochemical properties of nanoparticles such as size, shape and surface modifications can vastly alter the distribution and uptake of injected nanoparticles. Therefore, we aimed to provide an examination of the rapid size-dependent uptake of fluorescent PEG-modified polystyrene nanoparticles administered immediately following cardiac ischaemia-reperfusion injury in mice. By assessing the biodistribution of nanoparticles with core diameters between 20 nm and 2 μm 30 minutes after their administration, we conclude that 20-200 nm diameter nanoparticles are optimal for passive targeting of the injured left ventricle.