Objective: To determined whether the implementation of an intubation management protocol leads to the reduction of intubation-related complications in the intensive care unit (ICU). Design: Two-phase, prospective, multicenter controlled study. Setting: Three medical-surgical ICUs in two university hospitals. Patients: Two hundred three consecutive ICU patients required 244 intubations. Interventions: All intubations performed during two consecutive phases (a 6-month quality control phase followed by a 6-month intervention phase based on the implementation of an ICU intubation bundle management protocol) were evaluated. The ten bundle components were: preoxygenation with noninvasive positive pressure ventilation , presence of two operators, rapid sequence induction, cricoid pressure, capnography, protective ventilation, fluid loading, preparation and early administration of sedation and vasopressor use if needed. Measurements and main results: The primary end points were the incidence of life-threatening complications occurring within 60 min after intubation (cardiac arrest or death, severe cardiovascular collapse and hypoxemia). Other complications (mild to moderate) were also evaluated. Baseline characteristics, including demographic data and reason for intubation (mainly acute respiratory failure), were similar in the two phases. The intubation procedure in the intervention phase (n = 121) was associated with significant decreases in both life-threatening complications (21 vs. 34%, p = 0.03) and other complications (9 vs. 21%, p = 0.01) compared to the control phase (n = 123). Conclusions: The implementation of an intubation management protocol can reduce immediate severe life-threatening complications associated with intubation of ICU patients.