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To assess the diagnostic value of gadolinium (Gd) contrast administration in MRI follow-up examinations of patients with MS if the T2 lesion load is stable.We included 100 patients with MS with at least 2 cranial MRI follow-up examinations (mean follow-up time 4.0 ± 2.6 years). MRI was performed at 3 Tesla with a standardized protocol including T2-weighted, fluid-attenuated inversion recovery (FLAIR) and T1-weighted contrast-enhanced sequences. Images were analyzed for T2/FLAIR and contrast-enhancing (CE) lesions by 3 independent neuroradiologists. Isolated Gd-enhancing lesions without correlate in T2 and FLAIR images, and reactivated Gd+ lesions were further assessed for size and signal intensity.We identified a total of 343 new T2 lesions and 152 CE lesions in a total of 559 MRI follow-up examinations. New T2/FLAIR lesions were present in 30% of the scans. Of the Gd-enhancing lesions, 145/152 (95.4%) showed a correlate as a new T2/FLAIR lesion. There were 3 enhancing lesions (1.9% of all enhancing lesions) without T2/FLAIR correlate and 4 lesions (2.6%) that exhibited lesion reactivation or persistent enhancement over time. As a predictive factor of enhancement, we found that enhancing lesions had a higher T2 signal ratio (T2 SRlesion/normal-appearing white matter: 3.0 ± 0.1 vs 2.2 ± 0.1, p < 0.001).The likelihood of missing “active lesions” is overall small (1.7%) if T2 lesions are stable compared with the previous MRI examination. Lesion reactivation is rare. Our study indicates that Gd contrast administration might be dispensable in follow-up MRI of patients with MS if no new T2/FLAIR lesions and no new neurologic symptoms are present.