The use of microbiologic investigations in routine clinical practice, their value in guiding antibiotic prescription, and their influence on outcome were prospectively studied in 113 consecutive adults who developed ventilator-associated pneumonia (VAP). Blood cultures were performed in 78.7% of cases, protected specimen brushing in 95.5%, and bronchoalveolar lavage in only 45.1%. No causative agent was identified in 13 episodes (11.5%), and results of microbial tests directed a change in therapy in 43 (38.0%). Bronchoscopic results revealed inadequate initial selection of antibiotic therapy in 27 cases (23.9%) and led to a change in antibiotic treatment. Inadequate initial selection was still associated with a significantly greater increase in related mortality than adequate initial therapy (37.0% versus 15.4%, p < 0.05), although the change in therapy permitted clinical resolution in 17 (62.9%) of these 27 episodes, and 10 patients were discharged alive. Bronchoscopic results also permitted the reduction of the antibiotic spectrum in seven episodes (6.1%). This study suggests that in patients with VAP, bronchoscopic results are frequently associated with changes in antibiotic therapy. Nevertheless, our findings also emphasize the critical importance of an appropriate early antibiotic therapy.