Introduction: WellPrep (WP), a fully automated, one-step liquid-based cytol. (LBC) platform using an all-in-one closed chamber, has recently been developed as a next-generation LBC technol. This study aimed to evaluate the diagnostic performance and cytomorphol. features of WP regarding cervical cytol. and also to compare WP with the SurePath<sup>TM</sup> (SP), one of the most widely used LBC systems used worldwide. Methods: Cervicovaginal samples were taken from 212 females who enrolled in the study, and each sample was split and subsequently used for WP and SP LBC. Following the exclusion of seven cases with insufficient quality, a total of 205 cases were used for subsequent anal. Among them, 75 (36.6%) received histol. follow-up. All cases were interpreted according to the Bethesda System, while three experienced pathologists evaluated their cytomorphol. features. Results: The diagnostic concordance rate between the two LBC technologies was 84.4% (kappa = 0.776). Furthermore, the diagnostic concordance rates between SP and histol. and between WP and histol. were 73.3% (kappa = 0.516) and 70.7% (kappa = 0.497), resp. The two LBC methods showed comparable sensitivity, specificity, and area under the curve (AUC) for histol. HSIL (SP: sensitivity 82.8%, specificity 84.8%, and AUC 0.838; WP: sensitivity 79.3%, specificity 87.0%, and AUC 0.831). No significant difference was found regarding the sensitivity, specificity, and AUC between SP and WP (p = 0.586, p = 0.670, and p = 0.924, resp.). In terms of cytomorphol. features, WP revealed more often than SP the presence of coarse chromatin (p = 0.031) and mitoses (p = 0.008) but less commonly perinuclear clearing (p = 0.001). Conclusion: This is the first study demonstrating that WP has a comparable performance to SP. In conclusion, WP may be an alternative LBC technol. for cervical cancer screening.