Adrenocorticotropic hormone (ACTH) and corticosteroids are the usual first-line treatment options for infantile spasms. Despite significant differences, these agents are often lumped together in this context. There is a need to systematically explore the efficacy of corticosteroids in the treatment of infantile spasms, especially in comparison to ACTH. This review identified and analyzed corticosteroid clinical trials and summarized their short-term efficacy and tolerability. Primary outcome was cessation of spasms and abolition of hypsarrhythmia on prolonged video electroencephalographic monitoring. Eight corticosteroid clinical trials were found with only 2 fulfilling the criteria for adequate design. The weighted-mean efficacy of corticosteroids to achieve primary outcome was 31% for these 2 methodologically adequate studies. Including reanalyzed data from 3 other studies, the corticosteroid efficacy was found to be 42%. On the basis of the available evidence, the efficacy of high-dose corticosteroids is similar to low-dose ACTH and inferior to high-dose ACTH, the current standard treatment.