Purpose Within the last decade, SurePath and ThinPrep [both liquid-based cytology (LBC) tests] have replaced conventional cytology (CC) as primary test method in cervical cancer screening programs of multiple countries. The aim of our study was to examine the effect in the Dutch screening program. Methods All primary smears taken within this program from 2000 to 2011 were analyzed using the nationwide registry of histo- and cytopathology (PALGA) with a follow-up until March 2013. The percentage of smears classified as borderline/mildly dyskaryotic (BMD) and > BMD as well as CIN and cervical cancer detection rates were compared between SurePath and ThinPrep versus CC by logistic regression analyses (adjusted for age, screen region, socioeconomic status, and calendar time). Results We included 3,118,685 CC, 1,313,731 SurePath, and 1,584,587 ThinPrep smears. Using SurePath resulted in an increased rate of primary smears classified as > BMD [odds ratio (OR) = 1.12 (95% confidence interval (CI) 1.09-1.16)]. CIN I and II+ detection rates increased by 14 % [OR = 1.14 (95% CI 1.08-1.20)] and 8 % [OR = 1.08 (95% CI 1.05-1.12)]. Cervical cancer detection rates were unaffected. Implementing ThinPrep did not result in major alterations of the cytological classification of smears, and it did not affect CIN detection rates. While not significant, cervical cancer detection rates were lower [OR = 0.87 (95% CI 0.75-1.01)]. Conclusions The impact of replacing CC by LBC as primary test method depends on the type of LBC test used. Only the use of SurePath was associated with increased CIN II+ detection, although it simultaneously increased the detection of CIN I.