Background:Accurate prostate zonal segmentation on magnetic resonance images (MRI) is a critical prerequisite for automated prostate cancer detection. We aimed to assess the variability of manual prostate zonal segmentation by radiologists on T2‑weighted (T2W ) images, and to study factors that may influence it.Methods:Seven radiologists of varying levels of experience segmented the whole prostate gland (WG) and the transition zone (TZ) on 40 axial T2W prostate MRI images (3D T2W images for all patients, and both 3D and 2D images for a subgroup of 12 patients). Segmentation variabilities were evaluated based on: anatomical and morphological variation of the prostate (volume, retro‑urethral lobe, intensity contrast between zones, presence of a PI‑RADS ≥ 3 lesion), variation in image acquisition (3D vs 2D T2W images), and reader’s experience. Several metrics including Dice Score (DSC) and Hausdorff Distance were used to evaluate differences, with both a pairwise and a consensus (STAPLE reference) comparison.Results:DSC was 0.92 (±0.02) and 0.94 (±0.03) for WG, 0.88 (±0.05) and 0.91 (±0.05) for TZ respectively with pairwise comparison and consensus reference. Variability was significantly (p< 0.05) lower for the mid‑gland (DSC 0.95 (±0.02)), higher for the apex (0.90 (±0.06)) and the base (0.87 (±0.06)), and higher for smaller prostates (p < 0.001) and when contrast between zones was low (p< 0.05). Impact of the other studied factors was non‑significant.Conclusions:Variability is higher in the extreme parts of the gland, is influenced by changes in prostate morphology (volume, zone intensity ratio), and is relatively unaffected by the radiologist’s level of expertise.