Objective: A double-blind study was conducted to compare the performance of the new BestPrep® (CellSolutions) liquid-based thin-layer Papanicolaou (Pap) test with ThinPrep® (Hologic). Study Design: Samples from the study patients (n = 105) were collected twice in the same encounter with the ThinPrep sample always taken first and the BestPrep sample collected second. Slides were prepared according to both manufacturers' protocols and evaluated using manual microscopic review and the BestCyte® cell sorter imaging system (CellSolutions). Diagnostic truth for each case was determined by independent manual review of both slides by multiple pathologists and histology when available. The presence of atypical squamous cells of undetermined significance was the threshold for positive for sensitivity and specificity calculations. Results: BestPrep and ThinPrep, by manual review, had sensitivities for high-grade squamous intraepithelial lesion (HSIL) cases of 100 and 95.6%, respectively. Using the BestCyte cell sorter, both had 100% sensitivity. For the same HSIL cases, the digene HC2 high-risk human papillomavirus DNA test had sensitivities of 100% (BestPrep) and 95.6% (ThinPrep). Specificities were 71.4% (BestPrep) and 54.8% (ThinPrep). Conclusions: BestPrep was equivalent to ThinPrep for manual review even though BestPrep was always the second sample collected. The BestCyte cell sorter provides a practical alternative to manual review for both BestPrep and ThinPrep slides.