The purpose of this study was to determine the safety and cost-effectiveness of not routinely changing in-line suction catheters for patients requiring mechanical ventilation. Patients were randomly assigned to receive either no routine in-line suction catheter changes (n = 258) or in-line suction catheter changes every 24 h (n = 263). The main outcome measure was the incidence of ventilator-associated pneumonia. Other outcomes evaluated included hospital mortality, acquired organ system derangements, duration of mechanical ventilation, lengths of intensive care and hospital stay, and the cost for in-line suction catheters. Ventilator-associated pneumonia was seen in 38 patients (14.7%) receiving no routine in-line suction catheter changes and in 39 patients (14.8%) receiving in-line suction catheter changes every 24 h (relative risk, 0.99; 95% CI, 0.66 to 1.50). No statistically significant differences for hospital mortality, lengths of stay, the number of acquired organ system derangements, death in patients with ventilator-associated pneumonia, or mortality directly attributed to ventilator-associated pneumonia were found between the two treatment groups. Patients receiving in-line suction catheter changes every 24 h had 1,224 catheter changes costing a total of $11,016; patients receiving no routine in-line suction catheter changes had a total of 93 catheter changes costing $837. Our findings suggest that the elimination of routine in-line suction catheter changes is safe and can reduce the costs associated with providing mechanical ventilation.