INTRODUCTION: Acute pancreatitis has been extensively studied, however the effect of HIV status on outcomes has yet to be described. Here, we aim to assess the effects of positive HIV status on the mortality and overall outcomes in patients hospitalized with acute pancreatitis. METHODS: Data between 2008 and 2014 from the Nationwide Inpatient Sample database was extracted. Inclusion criteria for both groups included patients with a primary diagnosis of acute pancreatitis using International Classification of Diseases, 9th Revision codes and age greater than 17. Exclusion criteria included all ICD-9 codes for chronic pancreatitis and malignant pancreatico-biliary disorders and indeterminate HIV status. The study group consisted of patients with a primary diagnosis of acute pancreatitis and a concurrent diagnosis of HIV. In-hospital mortality was compared between the two groups. Univariate and multivariate analyses were used to generate odds ratios. Elixhauser Comorbidity scores predicting mortality and readmission were calculated based on weighted scores from 29 different comorbidities. Scores were compared between the two groups using univariate analysis. RESULTS: There were a total of 295386 patients with acute pancreatitis and no HIV and 2580 patients with acute pancreatitis and HIV for hospitals in the United States between 2008 and 2014. There was no significant difference in hospital mortality between acute pancreatitis with HIV and acute pancreatitis with no HIV on univariate analysis. There was a significant difference in hospital mortality on multivariate analysis for the HIV vs non-HIV groups (OR = 1.751, P = 0.011). HIV patients had a significantly higher Elixhauser mortality (5.72 ± 9.7) and readmission (31.63 ± 18.772) scores as compared to non-HIV patients' mortality (4.46 ± 8.58) and readmission (14.39 ± 13.28) scores P < 0.001, indicated a higher rate of comorbidities. CONCLUSION: Patients with HIV that are admitted with acute pancreatitis have a significantly higher mortality than those without HIV. We suspect the additional mortality may be due to an increased rate of comorbidities among HIV patients as evidenced by the greater Elixhauser scores. The higher rate of comorbidities among patients with HIV may be explained by a higher rate of infections and relative immunocompromised status compared to the non-HIV patients.