To evaluate the effect of MRI blood pool contrast agent on 4D flow image quality and ventricular volume measurements. Adult patients referred for clinical cardiac MRI (n = 22) were imaged with 4D flow. Patients with renal failure (n = 10) received ferumoxytol, and the remainder (n = 12) received gadofosveset trisodium. Image quality was assessed with (1) signal-to-noise ratio (SNR); (2) contrast-to-noise ratio (CNR); and (3) 5-point Likert scale based on endocardial border definition (1 = none; 2 = partial but unable to visualize; 3 = able to roughly estimate; 4 = visible for most of the cardiac cycle; 5 = excellent definition). A subset (n = 15) had short axis steady-state free precession (SSFP) cine imaging allowing for comparison of standard volumetric measurement technique with 4D flow derived volumetric measurements. 4D flow studies using ferumoxytol demonstrated a higher median Likert score of 5 (IQR, 5–5) versus 3 (IQR, 2–3). Median cavity SNR and CNR were higher for ferumoxytol compared to gadofosveset trisodium [65 (IQR, 50–74) versus 22 (IQR, 14–28), p < 0.001; and 40 (IQR, 32–49) versus 4 (IQR, 3–10), p < 0.001]. Good correlation (p < 0.001) was seen between SSFP and 4D flow measured ventricular volumes (ESV and EDV) with ferumoxytol (r = 0.998, mean difference = 1.2 mL, LOA = − 7.7–10.1 mL) and gadofosveset trisodium (r = 0.942, mean difference = − 2.7 mL, LOA = − 35.7–27.1 mL). Ferumoxytol used off-label as an MRI blood pool contrast agent offers an attractive alternative to gadofosveset trisodium in patients with renal failure, with excellent 4D flow image quality and good correlation of volumetric measurements compared to the CMR reference (SSFP).