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In daily practice, cytological diagnosis of serous effusion on conventional preparation can be challenging due to many drawbacks. SurePath liquid-based cytology (LBC) can improve diagnostic accuracy. The aim of the current study was to compare seven cytomorphological criteria, sensitivity and diagnostic accuracy between the conventional and BD SurePath LBC preparations in serous effusion samples.This retrospective study included 104 serous effusion samples. All materials were processed using both conventional cytological preparation and BD SurePath LBC technique. Clinicoradiological findings and previous histopathological or cytological reports were used as gold standards for final confirmed diagnosis.LBC preparation was more helpful in presenting a clear background, single cells, and loosely cohesive small monolayer sheets, better staining quality and less inflammatory cells (P<0.001). No significant difference was reported with regard to cellularity, cell distribution, and cellular details. Both techniques demonstrated similar diagnoses in 90 of 104 (84.1%) cases. The kappa statistics for the two methods was 0.087. The exact match of conventional cytology to the reference diagnosis was detected in 50 positive cases and 43 negative cases. SurePath LBC properly classified 56 positive and 40 negative cases. The diagnostic accuracy was 89.4 and 92.3% for conventional and LBC, respectively. Diagnostic accuracy for the combined techniques was 95.2%.BD SurePath technique has better staining quality, clean background with eliminated inflammatory cells, and predominance of single cells and monolayer sheets. SurePath LBC technique was associated with better sensitivity and overall diagnostic accuracy than conventional preparation. The combined preparations increased sensitivity and diagnostic accuracy compared with those with either method on its own.