h i g h l i g h t s Motor-evoked potential (MEP) gain is decreased in patients with amyotrophic lateral sclerosis (ALS). MEP gain may allow the early detection of upper motor neuron dysfunction in patients and improve the diagnosis of ALS. The diagnostic utility of MEP gain is equivalent to the triple stimulation technique (TST) and better than diffusion tensor imaging (DTI). a b s t r a c t Objective: The detection of upper motor neuron (UMN) dysfunction is necessary for the diagnosis of amy-otrophic lateral sclerosis (ALS). However, signs of UMN dysfunction may be difficult to establish. This study aimed to determine whether motor-evoked potential (MEP) gain (MEP area/background elec-tromyographic activity) represents an efficient alternative to assess UMN dysfunction. Methods: MEP area, MEP/compound muscle action potential (CMAP) area ratio, and MEP gain were tested at different force levels in healthy control subjects and ALS patients. Receiver operating characteristic (ROC) curve analyses was used to determine the diagnostic utility of MEP gain and compare it to alternative techniques, namely, diffusion tensor imaging (DTI) and the triple stimulation technique (TST). Results: MEP gain revealed a significant difference between the patients and healthy control subjects in contrast to MEP area and MEP/CMAP area ratio. The diagnostic utility of MEP gain was comparable with that of TST and superior to that of DTI. Conclusion: MEP gain can distinguish ALS patients from control subjects and may be helpful for the diagnosis of ALS. Significance: MEP gain appears to be a useful adjunct test and noninvasive method for the assessment of corticospinal dysfunction.