Unannounced telephone pill counts are an objective antiretroviral therapy adherence measurement tool, but this method has not been validated in young adults (YA) living with perinatal HIV infection. Perinatally infected YA, recruited from the Child and Adolescent Self-Awareness and Health Study, agreed to unannounced telephone pill counts to measure medication adherence over 4 months and phlebotomy to measure viral load (VL). Differences in pill count adherence scores among YA with a VL of ≤20 versus >20, and demographic differences were assessed. Participants (N = 62) were, on average, 24 years old; 57% were African American, and 40% were Latino. Participants with VL of ≤20 (60%) had significantly higher adherence scores (85% versus 62%; p = .004). Associations were not significant among older YA (range, 25-28 years) or Latinos. Unannounced telephone pill counts are a valid measure of antiretroviral therapy adherence in YA with perinatal HIV infection. Studies with larger samples are needed.