Infantile spasms (IS) have been conventionally treated with adrenocorticotropic hormone (ACTH), which is often associated with significant side effects. This study assessed the efficacy of vigabatrin (VGB) as an alternative in the treatment of IS and compared the efficacy of VGB in symptomatic vs cryptogenic patients. The study retrospectively reviewed 25 infants with IS (19 symptomatic, six cryptogenic) who were treated with VGB. Of the symptomatic group, 13 (68.4%) of 19 had clinical improvement, and 15 (78.9%) had electroencephalographic improvement. Three (50%) of six in the cryptogenic group had clinical improvement, and two (33%) had electroencephalographic improvement. Overall, three patients demonstrated clinical spasm control but electroencephalographic deterioration or persistence of hypsarrhythmia coupled with further cognitive decline. Four of the six partial clinical responders had deterioration of spasms with additional VGB dosage increases. VGB is comparable with ACTH in effectiveness for treatment of symptomatic IS. Higher doses of VGB may sometimes cause deterioration rather than further improvement, and therefore an optimum dosage of VGB needs to be titrated for every patient. Persistent electroencephalographic abnormalities and even electroencephalographic deterioration despite clinical control have been observed with VGB treatment; electroencephalographic monitoring during VGB treatment is recommended.