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The potential role of serum and alveolar procalcitonin as early markers of ventilator-associated pneumonia (VAP) and its prognostic value were investigated.Ninety-six patients with a strong suspicion of VAP were prospectively enrolled. VAP diagnosis was based on a positive quantitative culture obtained via a mini–bronchoalveolar lavage of 103 colony-forming units/ml or more. Blood and alveolar samples were collected for procalcitonin measurement and analyzed for diagnostic and prognostic evaluation on days 0, 3, and 6. Sensitivity, specificity, positive likelihood ratio, and receiver-operating characteristic curves were analyzed to define ideal cutoff values and approach the decision analysis.Serum procalcitonin was significantly increased in the VAP group (n = 44) compared with the non-VAP group (n = 52): 11.5 ng/ml (95% confidence interval, 5.9–17.0) versus 1.5 ng/ml (1.1–1.9). A serum procalcitonin concentration greater than 3.9 ng/ml (best cutoff value) was considered positive for the VAP diagnosis (sensitivity, 41%; specificity, 100%). Serum procalcitonin was significantly increased in the non-survivors compared with the survivors for the VAP group: 16.5 ng/ml (95% confidence interval, 8.1–24.9) versus 2.9 ng/ml (1.2–4.7). The best cutoff value for serum procalcitonin of the nonsurvivors in the VAP group was 2.6 ng/ml (sensitivity, 74%; specificity, 75%; positive likelihood ratio, 2.96). Regarding VAP diagnosis and prognosis, no significant differences were found for alveolar procalcitonin in all groups.Serum but not alveolar procalcitonin seems to be a helpful parameter in the early VAP diagnosis and an appropriate marker for predicting mortality.