Background: Plasmablastic Lymphoma (PBL) is a rare aggressive subtype of diffuse large B-cell lymphoma primarily affecting the immunocompromised, including those living with HIV. There is no established standard of care, and current survival estimates range from 8-15 months (mos). With the largest previous study of PBL limited to 590 patients (pts), we aimed to evaluate epidemiologic characteristics, treatment patterns and survival trends on a national scale. Methods: Pts diagnosed with PBL from 2010-2020 were identified in the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) Program. Age-adjusted incidence rates (IR) were calculated using SEER. Demographic and treatment characteristics and overall survival were evaluated in the NCDB using Kaplan-Meier and multivariate Cox regression analysis. Results: For the 1,153 pts identified in SEER, the incidence of PBL was 0.07 per 100,000 person-years, with higher IR in males (0.12) and pts age > 75 years (0.23). IR increased on average by 4.2% per year from 2010 to 2020 (95% CI 1.51-6.96). Of the 1,822 PBL pts in NCDB, the median age at diagnosis was 57 years. PBL was more common in male (77.2%) and White pts (76.8%). Most pts presented at an advanced (III or IV) Ann Arbor stage (59.9%). Pts were HIV+ in 50.2% of cases and 51.2% had extranodal disease. The median OS (mOS) was 22.4 mos (95% CI 16.2-28.6), with a 1-, 5-, and 10-yr OS of 56%, 40%, 32%, respectively. PBL pts treated with multiagent chemotherapy (N = 862, 66%) had mOS of 58.6 mos (95% CI 43.0-74.3). Pts who received no systemic treatment (N = 456, 25%) had mOS of 1.9 mos (95% CI 1.2-2.5). Pts with Stage I disease had a mOS of 86.2 mos, Stage II of 51.1 mos, Stage III of 35.9 mos, and Stage IV of 8.8 mos. Pts with HIV had a greater mOS (44.0 mos [95% CI 28.7-59.3]) than HIV- pts (21.7 mos [95% CI 12.4-30.9]). On multivariate Cox regression adjusted for age, race, and socioeconomic status, factors associated with worse OS included age (HR 1.03 [95% CI 1.02-1.04], p < 0.001), B symptoms (HR 1.35 [95% CI 1.11-1.65], p = 0.003) and advancing stage. Factors associated with improved OS included Hispanic ethnicity (HR 0.70 [95% CI 0.52-0.93], p = 0.014) and extranodal disease (HR 0.77 [95% CI 0.63-0.93], p = 0.001). HIV+ status had no significant impact on survival (HR 1.09 [95% CI 0.87-1.38], p = 0.443). Conclusions: We present the largest study to date describing the epidemiologic, survival, and treatment patterns of PBL. In contrast to prior studies, we found a longer mOS of 58.6 mos among those treated. This may represent a large real-world population providing more accurate estimates or reflect improved outcomes from a growing number of novel therapeutic options. Notably, HIV+ status did not have a significant impact on OS. While OS remains poor, advances in treatment over the last decade are promising and highlight the need for clinical advances to improve front line therapeutic options for PBL.