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Mesenchymal stem cells (MSCs) have shown therapeutic potential if successfully delivered to the intended site of myocardial infarction. The purpose of this pilot study was to test the feasibility of 111In oxine labelling of MSCs and single photon emission computed tomography (SPECT) imaging after intravenous administration in a porcine model of myocardial infarction. Adult farm pigs (n = 2) were subjected to closed chest experimental myocardial infarction. 111In oxine labelled MSCs (1×107 to 2×107 cells) were infused intravenously, and SPECT imaging was performed initially and on days 1, 2, 7 and 14. High quality SPECT images were obtained through 2 weeks of imaging. High initial MSC localization occurred in the lungs and slow progressive accumulation occurred in the liver, spleen and bone marrow. Renal activity was mild and persistent throughout imaging. No appreciable accumulation occurred in the myocardium. It is concluded that 111In oxine radiolabelling of MSCs is feasible, and in vivo imaging with SPECT provides a non-invasive method for sequentially monitoring cell trafficking with good spatial resolution. Because intravenous administration of MSCs results in significant lung activity that obscures the assessment of myocardial cell trafficking, alternative routes of administration should be investigated for this application.