Background: Parapneumonic effusions cause significant morbidity and mortality despite current developments in diagnostic and therapeutic approaches. Causative microorganisms may remain unidentified in a significant number of patients by cultures and Gram smears. Polymerase chain reaction ( PCR) is a molecular technique for the detection of causative bacteria; however, its efficiency in pleural fluids is less known. Objectives: The present study was performed to compare the efficiency of PCR in the detection of the three most common organisms ( Staphylococcus aureus, Streptococcus pneumoniae and Haemophylus influenzae) with conventional methods. Methods: Twenty-eight consecutive patients with parapneumonic pleural effusions were studied. On admission, pleural fluid samples were obtained for Gram staining, routine culture and PCR analysis for S. aureus S. pneumoniae and H. influenzae. Results: PCR analysis allowed detection of 11 microorganisms in 10 patients ( 35.7%), whereas pleural fluid cultures detected the etiological agent in only 2 (7.1%). S. pneumoniae was the most frequent agent. Conclusions: Pleural fluid cultures may have low diagnostic yields, partly due to prior antibiotic use. Pleural fluid PCR analysis may improve the etiologic diagnosis in parapneumonic pleural effusions, with technical advances leading to higher yields than obtained in this study. Copyright (C) 2007 S. Karger AG, Basel.