Background: Solid organ transplant (SOT) recipients are at increased risk for developing lymphoproliferative disorders and epithelial malignancies, owing largely to the effects of immunosuppression and oncogenic viral pathogens. This is the first population-based study to estimate the risk of Hepato-Pancreato-Biliary (HPB) cancer in this patient population. Methods: National Inpatient Database (NIS 1998–2010) was used to identify patients with heart, lung, liver, kidney and pancreas transplantation and demographic data were abstracted. The observed events for extrahepatic biliary, pancreatic and liver cancers were abstracted and converted to events/year/100,000 and compared against corresponding national incidence rates obtained from Surveillance Epidemiology and End Results (SEER) database. The Standardized Incidence Ratio (SIR) for each malignancy was calculated to assess the true risk. Results: 297,308 patients with SOT were identified in NIS database, of whom 1,189(0.4%) suffered from at least one HPB cancer. The mean age of SOT recipients with HPB cancer was 49.7 years similar to those without cancer (50.93). The male: female ratio of SOT patients with HPB cancer was 2.5:1. SOT and HPB cancer was highest in Caucasians. The in-hospital mortality was 9.8% in SOT patients with HPB cancer compared to those without cancer (2%). Liver transplant patients are at higher risk of developing extrahepatic biliary cancer (SIR: 119.18) and liver cancer (SIR 1092.97). Patients with heart, lung, kidney and pancreas transplantation have lower risk of HPB cancer compared to general population. Conclusion: Interestingly, only liver transplant recipients are at increased risk of developing HPB malignancies, compared to other SOT recipients. The findings of this study needs to be further validated to understand the risk difference of developing HPB malignancies in SOT recipients.Table 1Comparison of demographic characters of patients with solid organ transplantation (SOT) with and without hepatico-pancreato-biliary (HPB) malignanciesOverallSOT with HPB MalignancySOT without HPB MalignancyN (%)297,3081189 (0.4)296,119 (99.6)Age50.93 ± 16.849.72 ± 21.4750.93 ± 16.8Male: Female1.34:12.48:11.34:1Race Caucasian152,831 (51,4)654 (55.0)152,177 (51.4) African American37,578 (12.6)79 (6.6)37,499 (12.7) Hispanic28371 (9.5)130 (10.9)28,241 (9.5) Others78,528 (26.4)326 (27.4)78,202 (26.4)In-hospital mortality5985 (2.0)116 (9.8)5,869 (1.98)N: number of patients. Open table in a new tab Table 2Standardized incidence ratio of hepato-pancreato-biliary malignancies (HPB) in patients with solid organ transplantation (SOT)Extrahepatic biliary CaPancreatic CaLiver CaE1.912.58.6Heart TxO1.727.64.41SIR90.3560.8651.34Lung TxO0.722.96.54SIR38.223.2376.02Liver TxO2.269.9493.99SIR119.1879.531092.97Kidney TxO1.336.586.86SIR70.2152.6579.76Pancreas TxO03.241.08SIR025.9412.56E: Expected events/year/100,000, O: Observed events/year/100,000, SIR = Standardized Incidence Ratio (observed events/expected events × 100). Open table in a new tab N: number of patients. E: Expected events/year/100,000, O: Observed events/year/100,000, SIR = Standardized Incidence Ratio (observed events/expected events × 100).