bThe diagnosis of Legionnaires' disease (LD) is based on the isolation of Legionella spp., a 4-fold rise in antibodies, a positive urinary antigen (UA), or direct immunofluorescence tests. PCR is not accepted as a diagnostic tool for LD. This systematic review assesses the diagnostic accuracy of PCR in various clinical samples with a direct comparison versus UA. We included prospective or retrospective cohort and case-control studies. Studies were included if they used the Centers for Disease Control and Prevention consensus definition criteria of LD or a similar one, assessed only patients with clinical pneumonia, and reported data for all true-positive, false-positive, true-negative, and false-negative results. Two reviewers abstracted data independently. Risk of bias was assessed using Quadas-2. Summary sensitivity and specificity values were estimated using a bivariate model and reported with a 95% confidence interval (CI). Thirty-eight studies were included. A total of 653 patients had confirmed LD, and 3,593 patients had pneumonia due to other pathogens. The methodological quality of the studies as assessed by the Quadas-2 tool was poor to fair. The summary sensitivity and specificity values for diagnosis of LD in respiratory samples were 97.4% (95% CI, 91.1% to 99.2%) and 98.6% (95% CI, 97.4% to 99.3%), respectively. These results were mainly unchanged by any covariates tested and subgroup analysis. The diagnostic performance of PCR in respiratory samples was much better than that of UA. Compared to UA, PCR in respiratory samples (especially in sputum samples or swabs) revealed a significant advantage in sensitivity and an additional diagnosis of 18% to 30% of LD cases. The diagnostic performance of PCR in respiratory samples was excellent and preferable to that of the UA. Results were independent on the covariate tested. PCR in respiratory samples should be regarded as a valid tool for the diagnosis of LD.) is a life-threatening pulmonary infection. The most common species causing clinical disease in humans is Legionella pneumophila (1). In addition to L. pneumophila, 19 species are documented as human pathogens on the basis of their isolation from clinical specimens (2). LD can affect people both in the community (3) and in the hospital and, in both settings, can occur in outbreaks (4, 5). The true incidence of LD is difficult to assess, because the bacterial etiology for community-acquired pneumonia (CAP) is generally not documented in clinical practice. LD cannot be differentiated clinically or radiographically from CAP caused by other bacterial pathogens (6). As Legionella spp. are obligatory intracellular bacteria, they are unaffected by beta-lactam antibiotics and require specific treatment with high-dose quinolones or macrolides (7). Treatment providing coverage against Legionella spp. has been shown to improve clinical success (8). Thus, early diagnosis of LD is important and can have an effect on both public health and management in hospitals (9, 10).Conventional methods for the diagnosis of LD ...