Background: Pap testing has transitioned from conventional preparations (CP) to liquid-based preparations (LBP) due to perceived superiority of LBPs. Many studies conclude LBPs reduce unsatisfactory (UNSAT) tests, however some believe the evidence to substantiate this claim is weak. We studied the effect of the transition from CPs to LBPs on the proportion of UNSAT Pap tests (PT) in four health care systems in the United States. Methods: Our study cohort consisted of 548,174 women with 1,443,725 total PTs, ages 21-65 years, between 2000 and 2010. We used segmented regression analysis to estimate the effect of adopting LBPs on the proportion of UNSAT PTs. The effect of age on the rate of unsatisfactory PTs was also investigated. Results: Three sites implementing Surepath LBP experienced significant reductions in UNSAT PTs (Site 1 estimated effect: -2.46% [95% CI: -1.47%, -3.45%], Site 2: -1.78% [95% CI: -1.54%, -2.02%], Site 3: -8.25% [95% CI: -7.33%, -9.17%]. The fourth site implementing ThinPrep LBP did not experience a significant reduction in UNSAT studies. The relative risk of an UNSAT PT in women >= 50 increased after the transition to LBPs (Surepath: RR 2.1 [95% CI: 1.9, 2.2] and ThinPrep: RR 1.7 [95% CI: 1.5, 2.0]). Conclusions: We found that the strength of the effect of transitioning to LBPs on the proportion of UNSAT PTs varied with the proportion of unsatisfactory tests with CPs and the LBP platform used. The greatest reduction in UNSAT PTs is seen in women under 50.