Previous studies have addressed the issue of the usefullness of fast fluid-attenuated (fast-FLAIR), rapid acquisition relaxation-enhanced (RARE), and gradient spin echo (GRASE) sequences in small groups of patients with multiple sclerosis (MS). The aim of this study was to assess and compare the lesion volumes and the intra-rater reproducibility of such measurements using fast-FLAIR, dual echo RARE, and dual echo GRASE brain scans from a large sample of MS patients. Using a 1.5 Tesla scanner, fast-FLAIR, dual echo RARE, and dual echo GRASE scans (24 axial, 5-mm thick contiguous interleaved slices) of the brain were obtained from 50 MS patients. Total lesion loads (TLL) were assessed twice using a semi-automated local thresholding segmentation technique by the same rater from the scans obtained with the three techniques. Mean TLL were 20.3 mL for fast-FLAIR, 16.6 mL for RARE, and 17.6 mL for GRASE sequences. Mean TLL detected by the three techniques were significantly heterogeneous ( p < 0.001); at post-hoc analysis, the mean lesion volume detected on fast-FLAIR images was significantly higher than that on both RARE and GRASE images ( p < 0.001) and the mean TLL on GRASE scans was significantly higher than that on RARE scans ( p = 0.001). The mean values of intra-observer coefficient of variation for TLL measurements were similar for the three techniques (2.69% for fast-FLAIR, 2.33% for RARE, and 2.65% for GRASE). Our results confirm that fast-FLAIR sequences detect higher lesion volumes than those detected by other magnetic resonance imaging (MRI) sequences with shorter acquisition times. However, the reproducibility of TLL measurements is comparable among fast-FLAIR, RARE, and GRASE. This suggests that when assessing MS disease burden with MRI, the choice of the pulse sequence to be used should be dictated by the clinical setting.