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Background: MRI-based radiomics has shown promise in men with prostate cancer (PCa); however, successful clinical implementation is contingent upon on reproducible measurements. Purpose: We assessed the reproducibility of radiomics features extracted from bi-parametric prostate MRI (bpMRI) in prostate lesions and non-tumoral prostate tissue in men with PCa undergoing active surveillance (AS). Methods: This retrospective study included 47 men with biopsy-proven PCa undergoing AS (mean 68.9 ± 8.2 years, mean PSA density [PSAD] 0.08 ± 0.03 ng/mL/mL) who underwent two bpMRI approximately 12 months apart (range, 10-14 months; December 2018 to April 2020). The reproducibility of radiomics measurements was assessed using the same MRI platform (3T Skyra, Siemens Healthineers; inter-platform) (n = 37), different MRI vendors (Skyra, Siemens Healthineers; 3T Discovery MR750, GE Healthcare; inter-platform) (n = 10), and between observers (n = 10). Shape/1st-/2nd-order radiomics features were extracted from regions of interest on axial T2-weighted (T2-WI), diffusion-weighted imaging (DWI, b1600), and apparent diffusion coefficient (ADC) maps on prostate lesions, non-tumoral peripheral zones (PZs), and transition zones (TZs) using software. Reproducibility was evaluated by calculating the intraclass correlation coefficient (ICC) and coefficient of variation (CV). Associations of clinical variables and prostate volume were assessed. Results: PCa diagnoses included Gleason grade groups 1 (n = 46) and 2 (n = 1)]. Thirty-seven lesions (mean size 0.9 ± 0.4 cm) in 31 patients had PI-RADS v2.1 scores of 2 (n = 3)/3 (n = 12)/4 (n = 21)/5 (n = 1); 16 patients demonstrated diffuse PI-RADS 2 changes. Lesion radiomics features from T2-WI yielded a high proportion of good/moderate ICCs (intra-platform, 77.8%; inter-platform, 56.5%), whereas most DWI/ADC features yielded poor reproducibility. Similar results were observed for non-tumoral PZ/TZ. Intra-platform CVs were lowest for T2-WI lesion features (13.6%) and background PZ/TZ (<13.3%), while DWI/ADC exceeded 20%. Inter-platform CVs were lowest for lesions on T2-WI and were <18% for DWI/ADC; all background PZ/TZ CVs were < 16.4%. Inter-observer analyses showed good/moderate ICCs across all sequences and regions (57.4-92.6%). The distribution of ICC and CV values did not differ between intra- and inter-platform analyses (p > 0.05). Higher reproducibility (ICC > 0.5) was associated with larger prostate volume (intra-platform diagnostic odds ratio [DOR] = 2.58, 95% confidence interval [95%CI], 1.35-3.80, p = 0.01; inter-platform DOR = 3.48, 95%CI 1.79-5.17, p = 0.01) and older age (inter-platform DOR = 5.30, 95%CI 3.75-6.85, p < 0.01). Conclusions: Radiomics measurements from T2-WI demonstrated better intra-/inter-platform reproducibility than DWI/ADC for prostate lesions and non-tumoral tissue. Patient factors (larger prostate volumes and older age) influence radiomics stability. The optimization of diffusion-based radiomics features is needed to improve reproducibility given the essential role of DWI in prostate MRI.