Objective: To clarify the performance of liquid-based cytology (LBC) and conventional methods of preparing cervical specimens for cytological screening. Study Design: We studied 236,511 patients who participated in a population-based cervical cancer screening program conducted in the Niigata prefecture between 2005 and 2008. The percentage of unsatisfactory specimens and the disease detection rate were compared between specimens prepared by LBC and conventional methods. Results: (1) The LBC method demonstrated a significantly lower percentage of unsatisfactory specimens than the conventional method (1.38 and 11.45%, respectively; p < 0.01). (2) Among the initial women, tumor lesions were detected in 0.57% of those examined with the LBC method, which was significantly higher than the positivity rate of those examined with the conventional method (0.25%; p < 0.05). Among the women with repeat screening, disease was detected in 0.08% of those examined with LBC twice, which was significantly lower than the positivity rates for those examined with the conventional method followed by the LBC method (0.11%) or the conventional method twice (0.16%; p < 0.05). Conclusion: The LBC method is significantly more useful than the conventional method in terms of the low adequacy rate and the high detection rate of cancer in cervical cancer screening in a localized area in Japan.