Purpose Effective training of extracorporeal membrane oxygenation (ECMO) cannulation is key to fighting the persistently high mortality rate of ECMO interventions. Though augmented reality (AR) is a promising technology for improving information display, only a small percentage of AR projects have addressed training procedures. The present study investigates the potential benefits of AR-based, contextual instructions for ECMO cannulation training as compared to instructions used during conventional training at a university hospital. Methodology An AR step-by-step guide was developed for the Microsoft HoloLens 2 that combines text, images, and videos from the conventional training program with simple 3D models. A study was conducted with 21 medical students performing two surgical procedures on a simulator. Participants were divided into two groups, with one group using the conventional instructions for the first procedure and AR instructions for the second and the other group using instructions in reverse order. Training times, a detailed error protocol, and a standardized user experience questionnaire (UEQ) were evaluated. Results AR-based execution was associated with slightly higher training times and with significantly fewer errors for the more complex second procedure ($$p<0.05$$ p < 0.05 , Mann–Whitney U). These differences in errors were most present for knowledge-related errors, resulting in a 66% reduction in the number of errors. AR instructions also led to significantly better ratings on 5 out of the 6 scales used in the UEQ, pointing to higher perceived clarify of information, information acquisition speed, and stimulation. Conclusion The results extend previous research on AR instructions to ECMO cannulation training, indicating its high potential to improve training outcomes as a result of better information acquisition by participants during task execution. Future work should investigate how better performance in a single training session relates to better performance in the long run.