BACKGROUND: Malignant pleural effusion (MPE) is a common complication of advanced malignancy, but little is known regarding its prevalence and overall burden on a population level. METHODS: We conducted a retrospective analysis of MPE-associated hospitalizations using the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample, Agency for Healthcare Research and Quality (HCUP-NIS 2012). Cases were included if MPE was coded as a primary or secondary diagnosis or if an unspecified pleural effusion was coded in addition to a diagnosis of cancer with either of these being the primary diagnosis. RESULTS: A weighted sample of 126,825 admissions (0.35%) for MPE was identified among the 36,484,846 weighted admissions included in the database in 2012. Of these admissions, 70,750 (55.8%) were for female patients. The median age at admission was 68.0 years (interquartile range [IQR]), 58.4-77.2 years). Lung (37.8%), breast (15.2%), hematologic (11.2%), GI tract (11.0%), and gynecologic (9.0%) cancers were the most common primary malignancies associated with MPE. The median length of stay was 5.5 days (IQR, 2.7-10.1 days), and the inpatient mortality rate was 11.6%. Median hospitalization total charges were $42,376 (IQR, $21,618-$84,679). In the multivariate analyses, female sex, large fringe county residential area, Medicare insurance, and elective type of admission were independently associated with a lower risk of inpatient mortality. CONCLUSIONS: There is a considerable inpatient burden and high inpatient mortality associated with MPE in the United States, with potential demographic, geographic, and socioeconomic disparities.