Although noninvasive ventilation (NIV) use in severe acute exacerbation of COPD has substantially reduced the need for intubation, an important number of COPD patients still are mechanically ventilated through a tracheal tube in the ICU. Intubation is a major risk factor for lower respiratory tract colonization (LRTC) in ICU patients. Other risk factors for LRTC include colonization of the oral cavity, nasopharynx, and gastric content. Aspiration of contaminated oropharyngeal secretions is increased by supine position, underinflation of tracheal cuff, coma, and sedation. Tracheal tube biofilm formation plays an important role as a reservoir for microorganisms. Reduced cough reflex, altered mucocilliary clearance, hypersecretion and retention of mucus are frequent in COPD patients. In addition, malnutrition and corticosteroid use are common in this population resulting in altered cellular, and humoral immunity and higher risk for LRTC. Incidence of LRTC varies from 22-95% of intubated patients. Pseudomonas aeruginosa is the most frequently isolated microorganism at day 3 after intubation in COPD patients. LRTC is a major risk factor for ventilator-associated pneumonia, which is associated with increased mortality and morbidity in ICU patients. Several measures could be suggested to reduce LRTC in critically ill COPD patients. NIV use in severe acute exacerbations reduces the need for intubation. In addition, the early use of NIV averts respiratory failure after extubation and could reduce the duration of invasive mechanical ventilation. Other measures might be efficient in preventing LRTC such as semirecumbent position, avoidance of gastric distension, polyurethane-cuffed tracheal tubes, silver-coated tracheal tubes, subglottic aspiration, and continuous control of cuff pressure. Further studies should determine the impact of preventive measures aiming at preventing LRTC on outcome of COPD patients requiring intubation and mechanical ventilation in the ICU.