The use of superparamagnetic iron oxide (SPIO) for labeling cells holds great promise for clinically applicable cell tracking using magnetic resonance imaging. For clinical application, an effectively and specifically labeled cell preparation is highly desired (i.e. a large amount of intracellular iron and a negligible amount of extracellular iron). In this study we performed a direct comparison of two SPIO labeling strategies that have both been reported as efficient and clinically translatable approaches. These approaches are cell labeling using ferumoxides–protamine complexes or ferucarabotran particles. Cell labeling was performed on primary human bone marrow stromal cells (hBMSCs) and chondrocytes. For both cell types ferumoxides–protamine resulted in a higher percentage of labeled cells, a higher total iron load, a larger amount of intracellular iron and a lower amount of extracellular iron aggregates, compared with ferucarbotran. Consequently, hBMSC and chondrocyte labeling with ferumoxides–protamine is more effective and results in more specific cell labeling than ferucarbotran. Copyright © 2009 John Wiley & Sons, Ltd.