OBJECTIVE. The purpose of this study is to evaluate the magnetic susceptibility of normal- appearing white matter (NAWM) in patients with multiple sclerosis (MS) using quantitative susceptibility mapping. MATERIALS AND METHODS. Ninety-four patients with relapse-remitting MS (RRMS) (37 with gadolinium-enhancing lesions and 57 with only gadolinium-nonenhancing lesions) and 55 healthy control subjects were included in this retrospective study. The susceptibility values of NAWM relative to CSF in patients with MS were compared with those of white matter (WM) in healthy control subjects and were correlated with the patient status of gadolinium-enhancing lesions, disease duration, and expanded disability status scale scores. RESULTS. All 37 patients with RRMS and gadolinium-enhancing lesions also had gadolinium- nonenhancing lesions. Susceptibility values of NAWM in patients with MS and only gadolinium-nonenhancing lesions (-18.29 +/- 8.03 parts per billion [ ppb]) were higher than those for WM in healthy control subjects (-25.81 +/- 6.02 ppb; p < 0.001) and NAWM in patients with gadolinium-enhancing lesions (-25.64 +/- 6.55 ppb; p < 0.001). Susceptibility values of NAWM in patients with MS with gadolinium-enhancing lesions were similar to those for WM in healthy control subjects (p = 0.91). This trend was dependent on neither NAWM region nor disease duration when the data were controlled for age. NAWM susceptibility was not correlated with either disease duration or expanded disability status scale (p > 0.05). CONCLUSION. In patients with RRMS and gadolinium-nonenhancing lesions, the susceptibility values of NAWM decrease when gadolinium-enhancing lesions appear, approaching values similar to those of WM in healthy control subjects, suggesting that NAWM may contribute to the iron accumulation observed in early active MS lesions.