Background: Liquid-based cytology (LBC) for cervical cancer screening offers several advantages over conventional cytology. However, the extremely high cost of the current approved devices precludes widespread application of LBC technique in resource-constrained countries. This study aimed to evaluate the performance of an indigenous low-cost LBC technique, EziPREP™ (EP), against conventional preparations (CPs) for cervical cancer screening. Materials and Methods: A cross-sectional split-sample study with consecutive cervical sampling was conducted on 515 women attending the clinic at our institute. CP smears were prepared as per the standard technique using spatula and endocervical brush followed by detaching the head of brush into the fixative vial of EP. The EP samples were processed as per the manufacturer's protocol. Both CP and EP smears were stained using standard Papanicolaou stain protocol. Both sets of smears were evaluated for staining quality, morphologic details, and cytologic diagnoses. Cytologic diagnoses were correlated with cervical biopsy findings, wherever available. Performance characteristics of the two techniques were calculated. Results: The unsatisfactory rate for CP was 1.0%, while on EP, 1.3% smears had inadequate cellular material. The staining quality and morphological details were comparable in both sets of smears. The detection of infections and epithelial cell abnormality was more, though not statistically significant in EP smears. There was a 98% concordance in cytologic diagnosis between CP and EP smears. Cytohistologic concordance was observed in 96% of cases for both CP and EP smears. Although the time taken for processing and staining of smears was higher for EP (2.5 min for EP per smear and 1.6 min for CP per smear), the screening time reduced from 6.5 min per smear for CP to 2.2 min in EP smears. Conclusion: EP provides monolayered cervical smears with vivid morphological details, leading to reduced screening time and relatively higher pick-up of infections and low-grade cervical lesions as compared to conventional smears. The availability of such low-cost devices may enable wider application of cytology-based cervical cancer screening in low-resource countries.