In spite of the increasing number of children living with HIV in Nigeria, published data on their clinical profile are few. We describe the clinical profile at presentation of HIV-infected children at the University College Hospital, Ibadan, in a prospective study. Among 272 children studied (149 [54.8%] males; mean age 4.2 years [range 2 months to 15 years]), infection was acquired through vertical transmission in 252 (92.6%), blood transfusion in 5 (1.80%), and undetermined routes in 15 (5.5%) cases. Clinical features included weight loss (62.5%), prolonged fever (55.4%), generalized lymphadenopathy (48.6%), chronic cough (45.4%), and persistent diarrhea (28.3%). Tuberculosis was present in 45.3%, World Health Organization (WHO) clinical stages 3 and 4 disease in 70.6% and severe immunosuppression in 44.5% of cases. Pediatric HIV in Ibadan is acquired mainly vertically and most cases present with severe disease. Improved access to prevention services and early diagnosis are recommended.