Introduction: To increase middle molecule clearances, high-flux dialyzers with increased internal filtration have been developed. However, dialyzer design and structure may affect thrombin generation and platelet activation, thereby risking increased clotting and reduced dialyzer clearances. Methods: Coagulation parameters, platelet, white cell and endothelial activation markers were measured prior to and following dialysis sessions in 12 patients using two different dialyzers designed for increased internal filtration. Results: Prior to dialysis, patients had evidence of activation of coagulation with increased factor VIII:C, thrombin-antithrombin complexes and prothrombin fragment 1+2, increased platelet activation, with raised platelet factor 4, β-thromboglobulin levels and increased fibrinolysis (raised D-dimers). Dialysis was associated with the release of soluble platelet integrin, sP selectin, increased endothelial activation with increased levels of von Willebrand factor (vWF) antigen (vWF:Ag) and vWF propeptide (vWF:pp) and sE selectin. There was no difference in tinzaparin levels at the end of the dialysis session using either dialyzer, as shown by anti-Xa activity – 0.145 ± 0.027 versus 0.11 ± 0.017 IU/ml, respectively. Conclusion: Haemodialysis patients have an inflammatory phenoytype, characterized by increased activation of coagulation, platelets and also fibrinolysis. However, dialyzers designed to increase internal filtration did not significantly increase platelet activation or thrombin generation.