Extracorporeal carbon dioxide removal (ECCO2R) has gained widespread use as a supposedly less invasive alternative for hypercapnic respiratory failure besides venovenous extracorporeal membrane oxygenation (VV ECMO). Despite technological advances, coagulation-related adverse events remain a major challenge in both therapies. The overlapping operating areas of VV ECMO and pump-driven ECCO2R could allow for a device selection targeted at the lowest risk of such complications. This retrospective analysis of 47 consecutive patients compared hemostatic changes between pump-driven ECCO2R (n = 23) and VV ECMO (n = 24) by application of linear mixed effect models. A significant decrease in platelet count, increase in D-dimer levels, and decrease of fibrinogen levels were observed. However, except for fibrinogen, the type of extracorporeal support did not have a significant effect on the time course of these parameters. Our findings suggest that in terms of hemocompatibility, pump-driven ECCO2R is not significantly different from VV ECMO.