This study aimed at evaluating the influence of a different slice orientation on brain magnetic resonance imaging (MRI) lesion load in multiple sclerosis (MS). Fifteen MS patients were scanned obtaining both axial and sagittal conventional spin echo (24 slices; TR 2400, TE 30/80) brain MRI. The total lesion load (TLL) was assessed twice for each scan, using a semi-automated local thresholding technique and the same marked hardcopies. The mean TLL was 22734 mm3 for axial and 22003 mm3 for sagittal scans. The mean intra-observer coefficient of variation (COV) was 4.65% for the axial acquisitions and 4.52% for the sagittal acquisitions. This difference was not statistically significant (one-way ANOVA, P > 0.1). The lesion load was significantly higher from axial MRI as compared to the intra-observer variability (two-way ANOVA, P=0.01), but the fluctuations around this average difference between axial and sagittal scan TLL were significantly large (test for interaction, P < 0.001). Our data indicate that the use of sagittal conventional MRI scans does not seem to be worthwhile for the quantitative assessment of lesion load in MS patients.