Background Based on promising results over the past 10 years, the method of extracorporeal membrane oxygenation (ECMO) has developed from being used as a ‘rescue therapy’ to become an accepted treatment option for patients with acute lung failure (ARDS). Subsequently, the indication was extended also to patients suffering from cardiogenic and septic shock. Our aim was to evaluate hospital mortality and associated prognostic variables in patients with lung failure, cardiogenic, and septic shock undergoing ECMO. Furthermore, a cumulative sum (CUSUM) analysis was used to assess the learning curve of ECMO-treatment in our department. Methods We retrospectively analysed the data of 131 patients undergoing ECMO treatment in the intensive care unit of the Asklepios Hospital of Langen over the time period from April 2011 to July 2016. We categorised the patients into three groups: lung failure (n = 54); cardiogenic shock (n = 58); and septic shock (n = 19). The primary outcome variable was hospital mortality along with identification of prognostic variables on mortality before initiating ECMO using logistic regression. Second outcome variable was the learning curve of our department in patients with ECMO. Results 6-year hospital mortality was 54% in patients with lung failure, 59% in patients with cardiogenic shock, and 58% in patients with septic shock. The CUSUM analysis revealed a typical learning curve with a point of inflection in the year 2014. Patients treated before 2014 had a worse outcome (p = 0.04 whole cohort; p = 0.03 for lung failure). Furthermore, less than 20 treatments per year respectively treatment before 2014 were associated negatively with hospital mortality of lung failure patients showing an odds ratio of 4.04, as well as in the entire cohort with an odds ratio of 3.19. Conclusion For the first time, a steep ECMO-learning curve using the CUSUM tool has been described. Obviously, the experience with ECMO has to be taken into account when defining the role of ECMO in ARDS, cardiogenic, and septic shock.