Background Few reports have examined the feasibility of a post-contrast double inversion recovery (DIR) magnetic resonance (MR) sequence in patients with multiple sclerosis (MS) because of partial or complete signal loss of enhancing MS lesions. Purpose To compare subtracted images of DIR (pre-contrast – post-contrast DIR images) with contrast enhanced T1-weighted (CE-T1W) images in the depiction of contrast enhancement of MS lesions. Material and Methods In total, 27 patients were included. Two neuroradiologists interpreted both images of CE-T1W imaging and subtracted DIR, and interpretation of the images was classified into a score of 1–5 (from 5, definitely superior contrast of lesions on DIR subtraction compared to conventional CE-T1W imaging, to 1, definitely superior contrast of lesions on CE-T1W imaging. The interrater agreement (κ coefficient) was measured. The signal-to-noise ratio (SNR) and contrast-noise-ratio (CNR) of the lesion were compared. Results A significant difference ( P <  0.001) in scoring was seen between conventional CE-T1W imaging (2.1 ± 1.5 with one reviewer and 2.4 ± 1.5 with the other) and DIR subtraction (4.4 ± 1.0 with one reviewer and 4.7 ± 0.8 with the other). SNR from conventional CE-T1W imaging (24.8 ± 14.7) was significantly superior to that from DIR subtraction (4.0 ± 1.0; P <  0.001). CNR in DIR subtraction (326.4 ± 250.0) was significantly superior to that in conventional CE-T1W imaging (0.8 ± 5.5; P <  0.001). For interrater agreement in the evaluation of contrast enhancement of the lesions, κ coefficients were 0.84 for conventional CE-T1W imaging and 0.72 for DIR subtraction. Conclusion Subtracted DIR image enables more obvious contrast enhancement of the MS lesions compared with conventional CE-T1W imaging.