Purpose To compare cytology with cervicography in HIV-infected and uninfected adolescent females Methods At the time of analysis, 334 girls aged 13–19 years from 13 U.S. cities were participating in a prospective study of HIV infection. All subjects had cytology and a Cervigram™ (cervicography) performed at two consecutive visits 6 months apart, referred to as visit (V) 1 and 2. Cervigrams™ were sent to the parent company for diagnosis and were categorized as: “negative” or “positive” (compatible with low-grade or high-grade squamous intraepithelial lesions [SIL]). Cytology was considered abnormal if the subject had SIL at either V1 or V2. Sensitivity, specificity, and positive predictive value (PPV) of the Cervigram™ were calculated compared with repeat Papanicolaou (Pap) smears. Results Two consecutive adequate Pap smears were available for analysis in 200 adolescents; 51% (95% CI, 43–59) of the 142 HIV-positive youth and 19% (95% CI, 9–29) of the 58 HIV-negative youth had SIL on at least one Pap smear ( p < .001). A positive Cervigram™ was observed in 44% (95% CI, 36–53) of the HIV-infected group and 29% (95% CI, 17–41) of the HIV-uninfected group ( p = .06). For the HIV-infected group, the sensitivity, specificity, and PPV of the Cervigram™ to detect SIL were 58% (95% CI, 45–71), 69% (95%CI, 57–80), and 64% (95%CI, 52–77), respectively. For the HIV-uninfected group, the sensitivity, specificity, and PPV were 64% (95% CI, 31–89), 80% (95% CI, 65–90), and 44% (95% CI, 19–68), respectively. The combined sensitivity, using both the Pap smear and Cervigram™ result from V1 to detect SIL, was 82% (95% CI, 71–91 for HIV+ and 48–98 for HIV−) in both groups. However, the PPV based the performance of the Cervigram™ in Pap smear-negative women as 33% (95% CI, 17–53) and 15% (95% CI, 2–45) for the HIV-infected and uninfected group, respectively ( p = not significant [ns]). Conclusion Although the sensitivity of a single Pap smear increased significantly when the Cervigram™ was used as an adjunct, the low PPV in both HIV-infected and uninfected groups, suggests that cervicography has a limited utility for precancer and cervical cancer screening in high-risk adolescent populations.