Limited published data exist regarding the association of atrial fibrillation (AF) and acute pancreatitis. To test our hypothesis that AF increases mortality and clinical outcomes in patients with acute pancreatitis, we conducted a cross-sectional data review of the National Inpatient Sample (NIS) database. The NIS database was reviewed for the collection of data on patient hospitalizations in 2016 and 2017. Patients diagnosed with acute pancreatitis with and without concomitant AF were included in the analysis. The International Classification of Diseases, 10th revision coding system was used for the variables of interest. The Stata software program (StataCorp LLC, College Station, TX, USA) was used to perform statistical analyses. The chi-squared test or analysis of variance was used to identify differences in demographic characteristics between the groups. The study population included two groups of patients: those with acute pancreatitis only (n = 542,440) and those with both acute pancreatitis and AF (n = 32,790). The group with acute pancreatitis and AF had a two- to threefold higher rate of mortality [adjusted odds ratio (OR): 2.59; 95% confidence interval (CI): 2.04–3.28] and increased length of stay (adjusted OR: 1.28; 95% CI: 1.08–1.48). Also, significantly higher odds of sepsis (adjusted OR: 2.49; 95% CI: 2.06–3.01), congestive heart failure (adjusted OR: 3.16; 95% CI: 2.87–3.49), acute coronary syndrome (adjusted OR: 1.61; 95% CI: 1.17–2.21), stroke (adjusted OR: 3.94; 95% CI: 1.42–10.93), and acute kidney injury (adjusted OR: 1.42; 95% CI: 1.30–1.55) were observed in patients with acute pancreatitis and AF relative to in patients with acute pancreatitis only. Our results suggest AF increases mortality in patients with acute pancreatitis and that patients with acute pancreatitis and AF are at greater risk of worse clinical outcomes.