Circulating tumor cells get in contact with blood components including a bidirectional interaction with platelets. Platelets can be activated by tumor cells in order to protect them from the immune surveillance and to facilitate adherence to the vessel wall. Thus, impeding the tumor cell-platelet interaction should reduce metastasis. In this study, we use single cell force spectroscopy, an AFM-based technique, to quantify and characterize the effect of two drugs in a tumor cell-platelet interaction model: Tinzaparin (TZP) and Tirofiban (TRF). Tinzaparin is a low molecular weight heparin, consisting of polysaccharides with chain lengths up to 6kDa. Tirofiban is an inhibitor of the main platelet receptor glycoprotein IIb/IIIa (GPIIb/IIIa) used in some cases of myocardial infarction. The anticoagulant drug heparin was shown to reduce metastasis in animal models and clinical studies without clear knowledge about its mode of action. Tirofiban has never been evaluated in the context of metastasis before. Single cell force spectroscopy was performed with human non-small cell lung cancer cells (A549) and a dense layer of freshly isolated platelets. Force-distance curves were analyzed regarding maximum adhesion force (FA), total detachment work (WD), elasticity and tethering events. Tinzaparin (innohep®, Leo Pharma) and Tirofiban (Tirofiban Hexal®) were used in different concentrations to obtain dose-response-curves. Tinzaparin as well as Tirofiban reduced the tumor cell-platelet interaction significantly in a dose dependent manner: The maximal reduction of FA and WD was -33.1% and -41.6% for TZP (N=2-4 cells, n=42-111) and -28.6% and -48.2% for TRF (N=2-4, n=50-89) respectively. The sigmoid fit of the dose-response relations reveals an IC50 of 0.01-0.04 U/mL for TZP and an IC50 of 0.002-0.25 ng/mL for TRF. P-selectin was identified as target for TZP in paired experiments with TZP and anti P-selectin antibodies (N=6). Combined treatment with both drugs showed no additive effect on FA and WD (N=3). While both drugs do not alter significantly the elasticity of the involved cells, they show a decrease of membrane tether frequency (p<0.001, Mann Whitney test). Membrane tether analysis revealed that TZP and TRF caused largely identical tether distributions. These results indicate that both drugs target the same mechanism. We assume that the effect of TZP is attributed to the inhibition of P-selectin-induced outside-in signaling which prevents activation of GPIIb/IIIa. Our study quantified the inhibitory effect of TZP and TRF on the tumor cell-platelet interaction at the single cell level for the first time. Since the contact of tumor cells with platelets is thought to facilitate metastasis, our results suggest that Tinzaparin and Tirofiban have the potential to serve as antimetastatic drugs in low (subclinical) concentrations.