Objectives: Technical complications are a known hazard in veno-venous extracorporeal membrane oxygenation (vvECMO). Identifying these complications and predictive factors indicating a developing system-exchange was the goal of the study. Methods: Retrospective study on prospectively collected data of technical complications including 265 adult patients (Regensburg ECMO Registry, 20092013) with acute respiratory failure treated with vvECMO. Alterations in blood flow resistance, gas transfer capability, hemolysis, coagulation and hemostasis parameters were evaluated in conjunction with a system-exchange in all patients with at least one exchange (n=83). Results: Values presented as median (interquartile range). Patient age was 50(36-60) years, the SOFA score 11(8-14.3) and the Murray lung injury Score 3.33(3.3-3.7). Cumulative ECMO support time 3411 days, 9(6-15) days per patient. Mechanical failure of the blood pump (n=5), MO (n=2) or cannula (n=1) accounted for 10% of the exchanges. Acute clot formation within the pump head (visible clots, increase in plasma free hemoglobin (frHb), serum lactate dehydrogenase (LDH), n=13) and MO (increase in pressure drop across the MO, n=16) required an urgent system-exchange, of which nearly 50% could be foreseen by measuring the parameters mentioned below. Reasons for an elective system-exchange were worsening of gas transfer capability (n=10) and device-related coagulation disorders (n=32), either local fibrinolysis in the MO due to clot formation (increased D-dimers [DD]), decreased platelet count; n=24), or device-induced hyperfibrinolysis (increased DD, decreased fibrinogen [FG], decreased platelet count, diffuse bleeding tendency; n=8), which could be reversed after system-exchange. Four MOs were exchanged due to suspicion of infection. Conclusions: The majority of ECMO system-exchanges could be predicted by regular inspection of the complete ECMO circuit, evaluation of gas exchange, pressure drop across the MO and laboratory parameters (DD, FG, platelets, LDH, frHb). These parameters should be monitored in the daily routine to reduce the risk of unexpected ECMO failure.