Background: Patients with polyneuropathies typically have demyelination and/or axonal degeneration in peripheral nerves. Currently, there is a lack of imaging biomarkers to track the changes in these pathologies., Purpose: To develop and evaluate the reliability of a multiparametric quantitative magnetic resonance imaging (qMRI) method of peripheral nerves in the leg., Study Type: Prospective., Subjects: Seventeen healthy volunteers (36.2 ± 13.8 years old, 9 males) with 10 of them scanned twice for test-retest., Field Strength/sequence: 3 T, three-dimensional gradient echo and diffusion tensor imaging., Assessment: A qMRI protocol and processing pipeline was established for quantifying the following nerve parameters that are sensitive to myelin and axonal pathologies: magnetization transfer (MT) ratio (MTR), MT saturation index (MTsat), T 2 *, T 1 , proton density (PD), fractional anisotropy (FA), and mean/axial/radial diffusivities (MD, AD, and RD). The qMRI protocol also measures the volume of nerve fascicles (fVOL) and the fat fraction (FF) of muscles., Statistical Tests: The intersession reproducibility and inter-rater reliability of each qMRI parameter were assessed by Bland-Altman analysis and intraclass correlation coefficient (ICC). Pairwise Pearson correlation analyses were performed to investigate the intrinsic association between qMRI parameters. Distal-to-proximal variations were evaluated by paired t-tests with Bonferroni-Holm multiple comparison corrections. P < 0.05 was considered statistically significant., Results: The MTR, MTsat, T 2 *, T 1 , PD, FA, AD, and fVOL of the sciatic and tibial nerves, and the FF of leg muscles, had an overall good-to-excellent test-retest agreement (ICC varying from 0.78 to 0.99). All the qMRI parameters had good-to-excellent inter-rater reliability (ICC > 0.80). The data demonstrated a pattern of distal-to-proximal changes of an increased nerve MTsat and FA, and a decreased nerve T 1 , PD, MD, and RD, as well as a significantly increased muscle FF., Data Conclusion: The proposed multiparametric qMRI method of the peripheral nerves is highly reproducible and provided healthy control data which will be used in developing monitoring biomarkers in patients with polyneuropathies., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 2., (© 2023 International Society for Magnetic Resonance in Medicine.)