BACKGROUND AND PURPOSE: MR imaging studies have demonstrated that magnetic susceptibility in multiple sclerosis lesions is dependent on lesion age. The objective of this study was to use quantitative susceptibility mapping to determine whether lesions with a hyperintense rim, indicative of iron-laden inflammatory cells (rim +), follow a unique time-dependent trajectory of susceptibility change compared with those without (rim -). MATERIALS AND METHODS: We studied patients with MS with at least 1 new gadolinium-enhancing lesion and at least 3 longitudinal quantitative susceptibility mapping scans obtained between 1.1 and 6.1 years. Lesions were classified as rim + if a hyperintense rim appeared on quantitative susceptibility mapping at any time. A multilevel growth curve model compared longitudinal susceptibility among rim + and rim - lesions. RESULTS: Thirty-two new gadolinium-enhancing lesions from 19 patients with MS were included, and 16 lesions (50%) were identified as rim +. Quantitative susceptibility mapping rim + lesions were larger than rim + lesions with gadolinium enhancement (P = .001). Among all lesions, susceptibility increased sharply after enhancement to a peak between 1 and 2 years followed by a decrease. The overall susceptibility curve height for rim - lesions was 4.27 parts per billion lower than that for rim + lesions (P = .01). Rim - lesions demonstrated a higher linear slope relative to rim + lesions (P = .023) but faster cubic decay relative to rim + lesions (P = .005). Rim lesions started decaying approximately 2 years earlier compared with rim + lesions. CONCLUSIONS: There was a marked difference in the susceptibility temporal trajectory between rim + and rim + lesions during the first 6 years of lesion formation. Most rim + lesions retain iron for years after the initial lesion appearance.