Flail chest is associated with a higher morbidity compared with multiple rib fractures, and it requires early intubation. This was a prospective comparative uncontrolled study at an academic level 1 trauma center. Twenty-two patients with flail chest (FLAIL) were compared with 90 patients with more than two rib fractures but no flail chest (RIBS) to determine differences in outcomes such as mortality, significant respiratory complications (pneumonia and adult respiratory distress syndrome), need for mechanical ventilation, and length of hospital stay. Stepwise logistic regression identified independent risk factors of poor outcome. Despite similar age and rates of lung contusion and extrathoracic injury, FLAIL patients had a higher need for mechanical ventilation (86% versus 42%, P < 0.01), higher incidence of significant respiratory complications (64% versus 26%, P < 0.01), and longer hospital stay (28 +/- 21 versus 17 +/- 19 days, P = 0.04) compared with RIBS patients. Flail chest and extrathoracic injuries were independent risk factors of significant respiratory complications. Of 11 FLAIL patients who were not intubated on arrival, eight required intubation within the next 24 hours, often while receiving diagnostic studies in poorly monitored hospital areas; two of these patients suffered morbidity directly related to the delay in intubation. Three patients without associated injuries were managed successfully without intubation. Flail chest is an independent marker of poor outcome among patients with thoracic cage trauma. The majority of patients with flail chest need mechanical ventilatory support and develop significant respiratory complications. In the presence of associated injuries, intubation is unavoidable and should be done under controlled conditions early after arrival to avoid morbidity related to sudden respiratory decompensation.