Dendritic cells (DCs) represent an important linkage between the innate and adaptive immune system and express proinflammatory transcriptomic products early after trauma. The use of a genomic approach recently revealed that platelet factor 4 (PF4) is significantly upregulated in DCs in patients after multiple trauma. However, knowledge about subsequent PF4 alteration and its potential clinical relevance in the context of multiple trauma is still limited. We used quantitative reverse transcription-polymerase chain reaction to analyze PF4 expression in both myeloid DCs (MDCs) and plasmocytoid DCs (PDCs) isolated from 10 patients after multiple trauma. Intracellular PF4 as well as HLA-DR expression were detected by flow cytometry Furthermore, DCs and peripheral blood mononuclear cells were incubated on a monolayer of human umbilical endothelial cells and their adhesion properties were analyzed. The ratio of the DC subtypes (MDC and PDC) was assessed by flow cytometry. PF4 expression significantly increased on d 1 and d 2 as measured by reverse transcription-polymerase chain reaction. Intracellular PF4 content in MDCs and PDCs was significantly elevated in trauma patients compared with healthy controls. In addition, the surface antigen HLA-DR on MDCs was significantly elevated on d 1 and d 4 after trauma in patients compared with controls. However, cell adhesion of DCs did not show any significant differences between patients and controls. PF4 concentration in MDCs and PDCs significantly correlated with the injury severity score. These results confirm an early and subsequent posttraumatic activation of PF4 in DCs. PF4 also participates in the posttraumatic activation of DCs in relation to injury severity, a role that might be preferably based on the modification of receptor expression, whereas adhesion properties are largely unaffected.