Abstract Background Airway management is a key competence in emergency medicine. Patients heavily differ from those in the operating room. They are acutely ill by definition and usually not fasting. Evaluation of risk factors is often impossible. Current literature primarily originates from countries where emergency medicine is an independent specialty. We evaluated intubations in a high-volume emergency department run by internists and comprising its own distinctive intensive care unit. Methods In this prospective, noncontrolled, observational study, we continuously documented all intubations performed at the emergency department. We analyzed demographic, medical, and staff-related factors predicting difficulties during intubation using logistic regression models. Results For 73 months, 660 cases were included, 69 (10.5%) of them were without any induction therapy. Two hundred fifty-two (38.2%) patients were female, and their mean age was 59 ± 17 years. Three hundred four (49.9%) had an initial Glasgow Coma Scale of 3. Leading indications were respiratory insufficiency (n = 246; 37.3%), resuscitation (n = 172; 26.1%), and intracranial hemorrhage (n = 75; 11.4%). First attempt was successful in 465 cases (75.1%); alternative airway devices were used in 22 cases (3.3%). Time from the first intubation attempt to a validated airway was 1 minute (interquartile range, 0-2 minutes). Physicians' experience and anatomical risk factors were associated with failure at the first attempt, prolonged intubation, and the need for alternative devices. Conclusions Airway management at the emergency department possesses a high potential of failure. Experience seems to be the key to success.