We performed fast fluid-attenuated inversion recovery (fFLAIR) and conventional spin echo (CSE) brain MRI in 32 multiple sclerosis (MS) patients (eight each benign, relapsing-remitting, primary progressive, and secondary progressive). We compared number and site of lesions detected on each sequence. With initial separate assessment, we identified a total of 3,668 lesions-2,892 by CSE and 2,943 by fFLAIR. Following simultaneous review of the sequences, we identified an additional 217 lesions on fFLAIR and 229 on CSE. fFLAIR detected fewer lesions in the posterior fossa (66 versus 138, p = 0.001), fewer small (< 5 mm) discrete cerebral white matter lesions (671 versus 829, p = 0.0002), more subcortical lesions (542 versus 306, p < 0.0001), and more large discrete lesions (419 versus 385, p = 0.0006). Its relatively poor detection of posterior fossa lesions makes it premature for fFLAIR to replace CSE as the primary sequence for detecting MS lesions in clinical trials.