Background:Liquid-based cytology (LBC) preparation is a way to improve and refine the fine-needle aspiration (FNA) samples. There are a few studies comparing LBC with conventional smear (CS).Aim:The present study was undertaken to evaluate the utility of manual LBC (MLBC) and CS preparations in various FNA samples.Materials and Methods:In this cross-sectional study, a total of 100 FNA samples from various anatomical sites were evaluated using MLBC and CS preparations. Cellularity, blood, informative background, monolayers, cell architecture, cytoplasmic, and nuclear preservation were compared with MLBC and CS preparations by Wilcoxon signed rank test. P < 0.05 is considered statistically significant.Results:MLBC preparations were superior to CS preparations in view of absence of blood and debris (P = 0.001), presence of monolayers (P < 0.001), and preservation of cytoplasmic (P = 0.001) and nuclear details (P = 0.001). However, no statistically significant differences were found between MLBC and CS preparations with regard to cellularity (P = 0.157), informative background (P = 0.083), and architecture (P = 0.739).Conclusion:MLBC preparations in FNAC are a safe, easy, and less time-consuming procedure, and it may have promising diagnostic value in the evaluation of FNA samples from various anatomical sites. However, the use of both MLBC and CS preparations is recommended to achieve optimal diagnostic yield.