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Little is known about the course and management of perinatal tuberculosis (TB). We describe the presentation, medical and surgical management of culture-confirmed TB in infants younger than 3 months of age.We conducted a retrospective study including all infants younger than 3 months of age with culture-confirmed TB admitted to Tygerberg Hospital, Cape Town, South Africa, from March 2003 to June 2015.During the study period, 106 of 2017 (5%) children younger than 13 years of age with culture-confirmed TB were infants younger than 3 months of age. The median age on admission was 67 days (interquartile range, 40–79). Intrathoracic TB was present in 101 (95%) infants; of these, 34 (32%) had extrathoracic TB. Two (2%) infants had extrathoracic TB only, while 3 (3%) infants were asymptomatic and diagnosed as having TB infection only. Forty (38%) infants were HIV-exposed, and 14 (13%) were HIV-infected. The mother was identified as the source case in 53 (50%) infants. Mycobacterium tuberculosis was cultured in a median of 2 (interquartile range, 1–7) specimens per infant; 9 (9%) had drug-resistant TB. Bronchoscopy was done in 37 (35%) infants, and 27 (26%) underwent intrathoracic lymph node decompression. Twelve (11%) infants died during admission, 81(76%) were clinically stable on transfer or discharge from hospital, and outcome was not documented in 13 (12%) infants.TB in young infants often presents with severe intrathoracic disease, including airway compression. Bronchoscopy may aid confirmation of the diagnosis and management; decompression of intrathoracic lymph nodes was common. Mortality in this age group remains high.