BACKGROUND: Previous clinical data suggest that the presence of a pleural effusion is associated with poor survival. However, these studies were limited by either a small sample size or lack of an adequate control group. RESEARCH QUESTIONS: What is the impact of pleural effusion on survival in patients hospitalized with an admitting diagnosis of the three most common etiologies of pleural effusion: Cancer, congestive heart failure or pneumonia? STUDY DESIGN AND METHODS: This is a retrospective analysis of US veterans hospitalized between January 1 RESULTS: We analyzed 34,707 patients in the PE group and 792,217 patients in the NO-PE group. Patients with PE had a significantly higher all-cause mortality compared to patients with NO-PE. The median survival time was significantly lower in PE group as compared to NO-PE group across all three diagnosis, CHF (PE: 1.51 years
95% CI: 1.40-1.61 vs NO-PE: 3.23 years
95% CI: 3.21-3.26), Cancer (PE:1.33 years
95% CI 1.27,1.39 vs NO-PE: 2.05 years
95% CI:2.02-2.08) and pneumonia (PE: 4.27 years
95% CI: 3.94-4.61 vs NO-PE: 5.11 years, 95% CI: 5.06-5.15). The hazard ratio of all-cause mortality remained unchanged after adjusting for demographics and comorbidities. INTERPRETATION: The presence of a clinically significant pleural effusion was independently associated with higher all-cause mortality in patients with admitting diagnosis of CHF, cancer and pneumonia. Clinicians and researchers should consider the association of CHF, cancer, and pneumonia with pleural effusions when estimating the prognosis of individual patients and when assessing the survival of longitudinal cohorts.