Platelet activation and thrombus formation plays a critical role in acute thrombotic occlusion. Previous studies demonstrated the expression and enzymatic activity of the acid sphingomyelinase in platelets. Acid sphingomyelinase is secreted after activation of platelets. However, the role of acid sphingomyelinase in platelet physiology remained elusive. The present study thus investigated the role of acid sphingomyelinase (aSM) ibn platelets. To this end aSM-deficient (asm^-/-) mice and their corresponding wildtype littermates (asm^+/+) were isolated and subjected to functional analysis. In electron microscopy no differences in platelet morphology and granule biogenesis between asm^-/-- and asm^+/+-platelets was observed. However, according to FACS-analysis, confocal microscopy as well as in ELISA and luminescence measurements activation dependent secretion of a-granules (p-selectin), dense granules (ATP, serotonin) and lysosomes (b-hexoaminidase) after stimulation with different agonist concentrations was significantly blunted in asm^-/--platelets compared to asm^+/+-platelets. Aggregation was slightly decreased in aSM deficient platelets. In vitro flow chamber experiments under arterial shear rates (1700^-s) revealed a significant decrease in thrombus formation in asm^-/--platelets as compared to asm^+/+-platelets. In conlusion, the acid sphingomyelinase plays a role in the activation dependent platelet degranulation and thus influences thrombus formation.