Rapid pre-screening (RPS) is a useful tool to measure and improve performance in the cytology laboratory. Whether RPS is more or less effective in liquid-based cytology than in conventional smears is unknown. We compared the estimated sensitivity in a laboratory of 11 cytotechnologists which converted from conventional smears to SurePath™ (Becton Dickinson, Franklin Lakes, N.J., USA) liquid based cytology. In the 9 months prior to conversion, 23,286 smears were screened compared with 30,610 smears in the 12 months immediately after conversion. The estimated sensitivity of rapid pre-screening for 90 s improved significantly with liquid based cytology for all abnormalities (58.7 vs. 68.7%, p < 0.001), atypical squamous cells of undetermined significance + low-grade squamous intra-epithelial lesion (52.6 vs. 63.1%, p < 0.001), and high-grade squamous intra-epithelial alone (76.2 vs. 85%, p < 0.001). Histologic follow up for 156 cases identified by rapid pre-screening of SurePath slides showed 32 (21%) cases of CIN1 or greater and 18 cases (12%) with CIN3 or worse. We conclude that rapid pre-screening is significantly more sensitive in liquid-based cytology compared with conventional smears, and detects significant lesions that are missed by routine screening.