PURPOSE: Magnetic Resonance Lymphography (MRL) with ferumoxtran-10 as contrast agent has a high diagnostic accuracy in the detection of lymph node metastases in prostate cancer (PCa) patients, but ferumoxtran-10 is no longer available. Ferumoxytol may be an alternative. Our purpose was to compare the diagnostic accuracy of ferumoxytol-based MRL with ferumoxtran-10-based MRL. METHOD AND MATERIALS: Our dataset contained the MRL images from patients who had had two MRLs as part of their clinical work-up in 2009 or 2010: one with ferumoxtran-10 and one with ferumoxytol as contrast agent. Each MRL consisted of at least a 3D T1-weighted sequence and a 3D T2-weighted sequence. Two expert readers (an experienced radiologist and an experienced researcher), reading in consensus, interpreted each lymph node as normal or metastasized, based on the contrast uptake pattern in the T2-weighted images, and delineated the lymph nodes in both types of MRL. Based on these delineations, quantitative measurements of the contrast-induced signal decrease were performed using histogram analysis. Measurements of signal decrease inside the lymph nodes were used to discriminate metastatic from normal nodes. The areas under the receiver operating characteristic curves (AUC) were computed to compare diagnostic accuracy, and the statistical significance of the difference between the two contrast agents was tested using the R Project for Statistical Computing and the ROCKIT software package. RESULTS: A total of 57 lymph nodes from four patients were included in the analysis, of which 7 were metastatic. The AUC was 0.96 for ferumoxtran-10-MRL, which is similar to results found in previous studies, and 0.87 for ferumoxytol-MRL. The difference between ferumoxtran-10 and ferumoxytol was statistically significant (p<0.05). The difference between ferumoxytol-enhanced and non-enhanced imaging was also significant (p<0.01). CONCLUSION: Although the number of lymph nodes included in this pilot study is limited, our results show that the performance of ferumoxytol-MRL is significantly lower than ferumoxtran-10-MRL. However, ferumoxytol-MRL has still a significantly higher discriminative performance compared to plain MRI. CLINICAL RELEVANCE/APPLICATION: While ferumoxtran-10 performs best in the detection of nodal metastases but is not available, ferumoxytol improves accuracy compared to plain MRI and is recommended prior to PCa treatment planning.