A novel approach to generate left ventricular (LV) pressure–volume (PV) loops from combined 4D Flow MRI and computational fluid dynamics (CFD) is presented. Pressure was calculated from person-specific three-dimensional (3D) CFD models created from LV segmentations and peak-systolic pressure from the one-dimensional 111-artery CFD model, with aortic flow from 4D Flow MRI as input. Ten healthy volunteers underwent scan–rescan MRI. Additionally, one patient without cardiovascular abnormalities underwent MRI and invasive catheter measurement for single-case comparison. Scan–rescan reproducibility was very good overall, with no significant differences in any parameters and ICCs of all parameters but minimum pressure were significant and high (0.55–0.99). Aortic flow of 3D CFD model correlated well with 4D Flow (ICC = 0.74) and stroke volume of LV segmentation (ICC = 0.90). Segmentation volume variability resulted in 12% difference in stroke work and mean external power, while aortic flow variability resulted in 10–11% difference in most parameters. Single-case comparison is promising, with only 1.8 mmHg and 0.005 mmHg/mL difference in minimum pressure and EDPVR, and <10% differences for other parameters. Noninvasive pressure–volume loops can therefore reproducibly be generated from only aortic flow, cine short axis MRI, and brachial pressure measurement. Single-case comparison shows promise, but larger validation studies are needed.