Objectives: 4D (3D + time) indices of tissue impedance using power Doppler (PD) ultrasound (US) can be measured with spatialtemporal image correlation (STIC) imaging. We wished to evaluate their repeatability and their influence under changes to US machine settings and regional differences within the placenta. Methods: A total of 46 healthy women were recruited at 20-34 weeks of gestation. A total of 9940 3D frames from 644 4D data sets were analysed providing both 3D and 4D indices of vascularity. 4D vs. 3D indices were compared with different machine settings, across the cardiac cycle and in the different placenta regions to assess regional variability. Results: 3D and 4D indices significantly decreased as wall motion filter (WMF) was increased (P < 0.001). Repeatability decreased as WMF increased (ICC; low1 = 0.80; high1 = 0.60). Indices were significantly lower at the maternal aspect (P = 0.002-0.009) of the placenta and showed less repeatability (ICC; 0.42-0.79) than the fetal aspect (ICC 0.49-0.88). 4D repeatability was good in the central region (ICC 0.80-0.81) but poor in the periphery (ICC 0.45-0.59), while 3D indices were good and comparable between regions (ICC; 0.80 central; 0.81 peripheral). Conclusions: This study supports the future use of WMF 'low1' and PD to generate more reliable 4D indices values. For 3D indices, HD Flow may improve Doppler signal sensitivity. Regarding placental regional variability, the fetal plate and the central region demonstrated more repeatable 4D indices. 4D PD indices have potential to overcome the limitations of VOCAL TM indices and provide an internally standardised measure of localised impedance in vascular beds.