This study deals with the quantitative structure-activity relationship (QSAR) study of a series of 5-alkylidenepyridazine-3 (2H)-one as a novel non cAMP-based antiplatelet agent, using molecular descriptor derived from the 3D representation of the model with the CS Chem office version 8.0. Several types of molecular descriptor such as electronic, thermodynamic and steric have been used to derive a QSAR model between platelet inhibitory activity and structural properties. The best model for the prediction of platelet inhibitory activity was obtained by applying sequential multiple linear regression analysis method. Statically significant model with r ² > 0.87 was obtained by using ovality (OV), dipole moment on z-axis (DPL₃), HOMO energy (HE), standard Gibbs free energy (SGFE), total energy (TOE), torsion energy (TE) and non-1,4 VDW energy (NVDWE) descriptors. Regression coefficient of all descriptors used is significant at more than 99% level. Result shows that dipole moment DPL₃ and OV are the principle descriptors for the inhibition of platelet aggregations. The model was also tested successfully for internal q ² > 0.738 and external predictive r ² > 0.520 validation criteria. We demonstrate that the steric, topological and electronic descriptors play an important role in inhibition of platelet aggregation of the alkylidenepyridazin-3-ones.