Objective: To determine the relative sensitivity and specificity of the ThinPrep Pap Test, compared with the conventional Pap test in multisite study. Histology–cytology correlation was evaluated to determine specificity of the test. Methods: A total of 7,933 evaluable patients at eight separate clinical sites was screened for cervical abnormalities using the ThinPrep Pap Test. Results were compared with a historical control cohort of 16,261 patients from a similar patient population and with a similar patient profile who had received conventional Pap test screening. Results: Cytology results for each method showed that the ThinPrep Test significantly increased detection of low-grade intraepithelial lesions (LSIL) (112%) and high-grade intraepithelial lesions (HSIL) (116%), compared with the conventional Pap test. The atypical squamous cells of undetermined significance (ASCUS)/LSIL ratio was reduced in the ThinPrep group (1.2:1), compared with the conventional test group (2.1:1). Histology results confirm that increased sensitivity was not due to reduced specificity. ThinPrep reduced the SBLB rate to 10.5%, compared with the conventional Pap test rate of 18.5%. However, the ThinPrep rate of unsatisfactory specimens was 0.9%, compared with the conventional method. Cytology: ThinPrep Pap Test (TP) compared to conventional Pap Test (C Pap) Histology correlation Conclusions: In a multisite clinical outcomes trial, the ThinPrep Pap Test demonstrated significantly increased detection of low-grade and high-grade squamous intraepithelial lesions. Histology–cytology correlation data suggest that the increase in IISIL and LSIL detection represented a true increase in sensitivity without a loss of specificity. ThinPrep improved overall specimen adequacy.