The diagnosis of pneumonia in ventilated patients is exceedingly difficult. Although culture of tracheal aspirates have poor diagnostic value they are frequently used to diagnose ventilator-associated pneumonia (VAP). Recently a number of studies have reported on the diagnostic value of “blind” protected specimen brush (B-PSB) sampling in the diagnosis of VAP. B-PSB sampling can readily and safely be performed by respiratory care practitioners (RCPs). The aim of this study was to determine the cost-effectiveness of B-PSB sampling performed by respiratory therapists in patients with suspected VAP. During a 3-month run-in period, patients in our medical intensive care unit (MICU) with suspected VAP were treated based on clinical criteria and tracheal aspirate culture. Following this run-in period the house staff, nurses, and RCPs were prevented from sending tracheal aspirates for culture. All patients suspected of having VAP underwent B-PSB sampling with quantitative culture. The B-PSB sampling was performed by RCPs who had been trained to perform the technique. A PSB with a potential bacterial pathogen concentration greater than 500 CFU/ml was regarded as positive. During the 3-month run-in period 172 patients received mechanical ventilation with an average of 4.9 ±3.1 ventilator days/patient. During this period 79 patients were treated for VAP. During the 3-month study period 160 patients received mechanical ventilation, with an average of 5.1 ± 2.9 ventilator days/patient (NS). Fifty-eight B-PSB samplings were performed in 50 patients for suspected VAP. No complications related to the procedure were reported. No tracheal aspirates were cultured during this time period. Eight patients had positive PSB cultures. Antibiotics were changed in three of these patients based on the PSB results. Thirty-eight courses of antibiotics (in 36 patients) were stopped based on negative PSB results. Twelve cases of VAP were suspected in six patients receiving antibiotics for other reasons. No change in antibiotics were made in these cases based on the negative PSB results. The length of mechanical ventilation was 5.4 ± 3.2 days in the 38 culture-negative patients in whom antibiotics were stopped compared to 8.2 ± 4.7 days in the 8 patients with PSB-positive VAP (NS; p = 0.14). The direct cost savings as a result of discontinuing antibiotics was $9,500. There were additional cost savings due to the reduced number of culture specimens sent to the laboratory (approximately $3,000; taking the $23 cost of the PSB brush into account), with a projected annual cost savings of $50,000. B-PSB sampling is a simple and cost-efficient diagnostic test that can safely be performed by adequately trained RCPs. Furthermore, this study confirms that antibiotics may be safely discontinued in patients with negative quantitative culture results.