Background: Ketogenic diet can be an effective alternative therapy for medication refractory infantile spasms. Infantile spasms are more prevalent in children with Down syndrome compared with the general population and often medication refractory. Methods: Charts of infants who presented to the Children’s Hospital of Eastern Ontario with Down syndrome and refractory infantile spams treated with ketogenic diet from 2012 to 2025 were reviewed. Clinical response defined by cessation of epileptic spasms and resolution of hypsarrhythmia. Diet ratio,tolerance, side effects, concomitant medications, and diagnostic tests were evaluated. Results: 5 infants were treated with ketogenic diet after failing first line anticonvulsant mendications: viagabatrin and corticosteriods. Ketogenic diet was viable only via G-tube in 1 patient and by NG tube in 3 due to risk of aspiration. Diet was compatible with second line anticonvulsants. Complete electroclinical response occurred in 2 infants after 4 weeks. Partial seizure reduction and electrographic improvement was observed in 1 infant. 1 patient died due to unrelated respiratory illness. Conclusions: Ketogenic diet is a viable potentially effective therapeutic option for infants with Down syndrome and medication refractory infantile spasms. These infants present challenges inherent of Down syndrome such as hypotonia, higher risk for aspiration which need to be considered before diet introduction.