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Aim: To better understand the aetiologies of epileptic spasms in infants, as well as the safety and efficacy of high dose corticosteroids in tuberculosis and human immunodeficiency virus (HIV) endemic resource‐limited settings. Method: This was a retrospective analysis of infants with epileptic spasms managed at the tertiary referral centres in the Western Cape, South Africa. Results: Of 175 children with epileptic spasms, the median age at onset was 6 months (interquartile range 4–8 months). Structural aetiologies were most common (115 out of 175 [66%]), with two‐thirds related to perinatal insults. A lead time to treatment (LTTT) of less than 1 month was more likely in the epileptic encephalopathy/developmental and epileptic encephalopathy (DEE) group: 58 out of 92 (63%), compared to 28 out of 76 (37%) of those with developmental encephalopathy (p = 0.001). Failure to recognize preceding developmental delay was common. Ninety‐nine children (57%) received first line hormonal therapy such as adrenocorticotropic hormone. A total of 111 out of 172 children (65%) from the developmental encephalopathy and epileptic encephalopathy/DEE groups had clinical and/or electroencephalogram resolution of spasms within 14 days. In our population, children in whom an aetiology could not be identified were statistically more likely to have moderate to profound developmental delay at 1 year of age: 33 out of 44 (p = 0.001). Based on reported incidence of epileptic spasms, 23 to 58 cases per annum would be expected but a far smaller proportion presented to our centres. Interpretation: Whilst this is the largest cohort of infants with epileptic spasms from sub‐Saharan Africa, the study size is less than expected; this may reflect misdiagnosis and failure of referral pathways. Despite a reported shorter LTTT, infants with DEE had worse developmental outcomes compared to international studies. Hormonal therapy was safe and effective in our setting, despite exposure to high levels of tuberculosis and HIV. What this paper adds: The number of unreferred cases of epileptic spasms in South Africa remains high.Caregivers and health care workers in primary care facilities often fail to recognize developmental delay.The burden of disease from hypoxic‐ischaemic encephalopathy remains high in our resource‐limited setting.Hormonal treatment (e.g. adrenocorticotropic hormone) was safe and effective despite the high prevalence of human immunodeficiency virus and tuberculosis. [ABSTRACT FROM AUTHOR]