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To develop and measure the reproducibility of 4-min whole brain myelin water fraction (MWF) mapping using fast acquisition with spiral trajectory and T2prep (FAST-T2) sequence at 3T.Experiments were performed on phantoms, 13 volunteers, and 16 patients with multiple sclerosis. MWF maps were extracted using a spatially constrained non-linear algorithm. The proposed adiabatic modified BIR-4 (mBIR-4) T2prep was compared with the conventional composite T2prep (COMP). The effect of reducing the number of echo times (TEs) from 15 to 6 (reducing scan time from 10 to 4 min) was evaluated. Reproducibility was assessed using correlation analysis, coefficient of variation (COV), and Bland–Altman plots.Compared with COMP, mBIR-4 provided more accurate T2 in phantoms and better MWF maps in human brains. Reducing the number of TEs had a negligible effect on MWF map quality, with a regional MWF difference of <0.8%. Regional MWFs obtained by repeated scans showed excellent correlation (R = 0.99), low COV (1.3%–2.4%), and negligible bias within ±1% limits of agreement. On a voxel-wise basis, the agreement remained strong (correlation R = 0.89 ± 0.03, bias = 0.01% ± 0.29%, limits of agreement = [−3.35% ± 0.73%, 3.33% ± 0.61%]).Whole brain MWF mapping with adiabatic FAST-T2 is feasible in 4 min and provides good intrasite reproducibility. Magn Reson Med 76:456–465, 2016. © 2015 Wiley Periodicals, Inc.