Background: Magnetic resonance imaging (MRI) is used to diagnose and monitor disease activity in relapsing-remitting multiple sclerosis (RRMS). The objective of this study was to explore the association of “ultrabright” axial fluid-attenuated inversion recovery (FLAIR) lesions with gadolinium enhancement in patients with RRMS using qualitative and quantitative approaches. Methods: MRIs from patients with RRMS from 2010 to 2015 were reviewed. Two radiologists independently identified ultrabright lesions on axial FLAIR sequences. The contrast-to-noise ratio (CNR) was measured for ultrabright and control lesions. Results: Of 301 lesions included in the study, 77 (26%) were identified by both radiologists as ultrabright. Interrater agreement was moderate (κ = 0.77, P < .001). Lesions identified by both radiologists as ultrabright demonstrated an association with gadolinium enhancement (χ21 = 30.8, P < .001) but were not associated with MRI magnet strength (χ21 = 0.24, P = .65). Higher CNR values were associated with gadolinium enhancement for 1.5-T studies (OR, 1.05; 95% CI, 1.02–1.07; P = .001) and 3-T studies (OR, 1.02; 95% CI, 1.02–1.03; P < .001). Diagnostic accuracy of the quantitative model was good for 1.5-T studies (area under the curve, 0.79; 95% CI, 0.68–0.9; P < .001) and 3-T studies (area under the curve, 0.78; 95% CI, 0.73–0.84; P < .001). Positive predictive value of 100% was obtained for CNR values of 92 for 1.5-T and 184 for 3-T studies. Conclusions: Qualitatively and quantitatively identified ultrabright axial FLAIR lesions are significantly associated with gadolinium enhancement.