The objective of this study was to examine characteristics of long-term survivors (aged 5 years or older) of vertical human immunodeficiency virus (HIV) infection. A retrospective cohort study design was employed. Forty-eight (68%) of 71 children who were born before 1990 and evaluated in our center survived to at least 5 years of age; 41 (58%) children remain alive (median age, 7.3 years). Only one (11%) of nine children with initial acquired immunodeficiency syndrome (AIDS)-defining conditions in the first year of life survived to age 5, whereas 47 (76%) of 62 children who did not have AIDS by age 1 year were alive at 5 years of age (p = .0003). Seventeen (43%) of 40 children with AIDS-defining conditions before age 5, and all 31 children without such conditions, survived to age 5 years (p = .000001). All eight children with lymphoid interstitial pneumonitis/pulmonary lymphoid hyperplasia (LIP/PLH) as their sole AIDS-defining condition survived to age 5. All 24 children who had neither an AIDS-defining condition nor severe immunosuppression by 5 years of age, and 24 (51%) of 47 children who had either or both of these findings, survived to age 5 years (p = .00008). To date, only 16 (39%) of 41 surviving children older than 5 years of age have had an AIDS-defining condition. However, true nonprogression of HIV disease (no clinical signs or symptoms; no evidence of immunosuppression) was unusual, occurring in only two (5%) of the same 41 children. In our center, most children with vertical HIV infection survive to at least 5 years of age, but the prognosis is not as good for those who experience an AIDS-defining condition or severe immunosuppression in the first 5 years of life.