Background <p>Research exploring the relationship between atrial fibrillation (AF) and acute pancreatitis (AP) is limited. This study aims to explore the association between AF and both the disease severity and in-hospital mortality in AP.</p> Methods <p>This research included a total of 3,537 eligible patients with AP from three medical centers. Participants were categorized into two groups: those with a history of AF and those without (non-AF group). Binary multivariable logistic analysis was employed to examine the relationship between AF and outcomes. Sensitivity analyses, including multinomial logistic regression, stabilized inverse probability treatment weighting (sIPTW) analyses and the calculation of the <i>E</i> value, are conducted to assess the robustness of our findings.</p> Results <p>A total of 122 patients, representing 3.45% of the cohort, had a history of AF. Binary multivariable analyses indicated that AF is independently associated with increased disease severity, but no significant association was found with in-hospital mortality. Sensitivity analyses demonstrated that the results obtained from the sIPTW analyses were consistent with those derived from the multivariable analyses. Furthermore, an evaluation of the <i>E</i> value suggests that the potential impact of unmeasured confounders on the association between AF and both in-hospital mortality and disease severity is likely to be minimal.</p> Conclusions <p>Our research indicates that AF is independently associated with the increased disease severity; however, it may not increase the risk of in-hospital mortality in patients with AP.</p>