BACKGROUND: This study was conducted tocompare studies of pleural and peritoneal effusion, assess the quality and diagnostic features between conventional and cell block preparation and evaluate the role of cell block to be used along with conventional smear for routine cytological practice. METHODS: This was a hospital-based cross-sectional study conducted in tertiary care center among 168 samples to compare conventional smears with cell block preparation in increasing the sensitivity of cytodiagnosis of pleural and peritoneal fluids received in the cytology laboratory at the Department of Pathology, Tertiary Care Hospital over the period of two years. RESULTS: In contrast to just 3.6% in traditional smears, 46.4% of instances displayed extensive cellularity on cell blocks. In cell blocks, the proportion of instances exhibiting minimal or nonexistent cellularity drops from 95% in conventional smears to 3%. While the percentage of cells with appropriate cellularity was lower in cell block (50.6%) than in conventional smear (86.9%), the statistical difference was still significant. The mean value of different cytological parameters in the CB is comparatively higher than in CS and this difference is found to be significant statistically. The frequency of malignant cells detected by the cell block technique was higher than that of the conventional smear (n = 14 versus n = 8), and this difference was also found to be statistically significant when comparing the two cytodiagnostic methods for the final diagnosis of specimens. CONCLUSION: To sum up, a combination of the cell block technique and conventional smears should be utilized not just for questionable effusions on conventional smears but also as a standard procedure for all effusions received in order to uncover concealed cases of cancer or other diseases. For labs with low resources that can manufacture cell blocks utilizing plasma thromboplastin in an economical manner, this method is ideal.