AbstractPurposeTo demonstrate proof‐of‐concept of a T₂*‐sensitized oxygen‐enhanced MRI (OE‐MRI) method at 3T by assessing signal characteristics, repeatability, and reproducibility of dynamic lung OE‐MRI metrics in healthy volunteers.MethodsWe performed sequence‐specific simulations for protocol optimisation and acquired free‐breathing OE‐MRI data from 16 healthy subjects using a dual‐echo RF‐spoiled gradient echo approach at 3T across two institutions. Non‐linear registration and tissue density correction were applied. Derived metrics included percent signal enhancement (PSE), ∆R₂* and wash‐in time normalized for breathing rate (τ‐nBR). Inter‐scanner reproducibility and intra‐scanner repeatability were evaluated using intra‐class correlation coefficient (ICC), repeatability coefficient, reproducibility coefficient, and Bland–Altman analysis.ResultsSimulations and experimental data show negative contrast upon oxygen inhalation, due to substantial dominance of ∆R₂* at TE > 0.2 ms. Density correction improved signal fluctuations. Density‐corrected mean PSE values, aligned with simulations, display TE‐dependence, and an anterior‐to‐posterior PSE reduction trend at TE₁. ∆R₂* maps exhibit spatial heterogeneity in oxygen delivery, featuring anterior‐to‐posterior R₂* increase. Mean T₂* values across 32 scans were 0.68 and 0.62 ms for pre‐ and post‐O₂ inhalation, respectively. Excellent or good agreement emerged from all intra‐, inter‐scanner and inter‐rater variability tests for PSE and ∆R₂*. However, ICC values for τ‐nBR demonstrated limited agreement between repeated measures.ConclusionOur results demonstrate the feasibility of a T₂*‐weighted method utilizing a dual‐echo RF‐spoiled gradient echo approach, simultaneously capturing PSE, ∆R₂* changes, and oxygen wash‐in during free‐breathing. The excellent or good repeatability and reproducibility on intra‐ and inter‐scanner PSE and ∆R₂* suggest potential utility in multi‐center clinical applications.