In order to determine the potential indications of transthoracic needle aspiration (TNA) using the ultrathin 25G needle for the diagnosis of nonopportunistic lung infections, we prospectively analyzed the diagnostic efficacy, safety, and therapeutic implications of its results in 97 patients with nonventilated nosocomial pneumonias (NVNP). The sensitivity of TNA was 60.9%. Specificity and positive predictive value (PPV) were 100%. Negative predictive value (NPV) was 34.1%. The complications in the studied cases were nil in 89 cases (91.8%), transient hemoptoic expectoration (< 10 ml) in five (5.2%), and self-limited partial pneumothorax in three (3.1%). No complications needing treatment were observed. On the basis of a positive TNA result, the initial antibiotic treatment was modified in 29 of 97 (29.9%) cases. In twelve of these, the empirical antibiotic regimen was demonstrated to be ineffective. We conclude that, using the 25G needle, TNA has a good diagnostic efficacy and is a safe procedure for the etiologic investigation of NVNP. A positive TNA result has significant therapeutic relevance, even in cases where broad-spectrum antibiotics are empirically prescribed.