OBJECTIVES: Malignant Pleural Mesothelioma (MPM) is a rare, aggressive cancer with poor prognosis, currently accounting for 0.10% deaths annually in the United States (U.S.). The current treatment options are limited, including surgery and chemotherapy with pemetrexed, cisplatin, and bevacizumab. There is limited recent information on disease epidemiology and baseline estimates of occurrence and characteristics in a large U.S. cohort. Therefore, the objective of this analysis was to describe the long-term trends in incidence rates and survival in MPM. METHODS: The prevalence, incidence, and overall survival of MPM patients by sex, year of diagnosis, and geographical location for all races were evaluated using data from 18 cancer registries with SEER from 1973-2013 for MPM patients by ICD-O code 9050/3 and C38.4. Cancer-directed surgery and outcomes were also examined over time. RESULTS: The prevalence of MPM increased with age, but decreased over time. Age-adjusted incidence rates per 100,000 were higher in patients 65 years and older (3.0) vs 24-64 years old (0.1), and in males (0.9) vs females (0.2). Incidence rates were higher in geographical locations with higher asbestos exposure. The incidence of patients receiving surgery per 100,000 decreased over time, from 1.2 to 0.43. Observed survival was lower in patients greater than 65 years old, with a median survival of 1 year, and remained relatively unchanged after the FDA approval of pemetrexed in 2004. CONCLUSIONS: The trend in prevalence rates demonstrates a delay in disease onset from asbestos exposure to disease diagnosis. This decrease in prevalence over time is expected with stringent laws imposed around asbestos usage and removal. Very few patients received surgery, which suggests a higher usage of chemotherapy. There was minimal change in survival before and after the FDA approval of pemetrexed for MPM, demonstrating an unmet need for additional treatment options.