Various methods exist in the clinical practice of long-term venovenous (VV) extracorporeal life support (ECLS). Among the clinical techniques used are single venous access with a dual-lumen catheter, and cannulation of the jugular and femoral veins. Tidal flow VV ECLS uses a single-lumen catheter to achieve both venous drainage and arterialized reinfusion through a series of tubing occluders that are automated by a pump. A single venous occluder tidal flow system with a 15 Fr single-lumen cannula (n = 6) and passive filling M pump was compared to a conventional 14 Fr dual-lumen cannula (n = 7) and roller pump for four hours of VV ECLS. The changes in platelet count and plasma-free hemoglobin (pHgb) were compared. The results showed a decline in platelet counts typical of ECLS in both groups that were not significantly different from each other. A small elevation in pHgb did not rise above normal clinical levels of 15 mg/dL in either group after four hours of ECLS. Some recirculation was observed and needs to be addressed in future studies. Single occluder tidal flow ECLS may be feasible and efficacious for long-term application once recirculation is resolved and the system evaluated for long-term support.