Background <p>The association between red blood cell distribution width (RDW) and short- and long-term all-cause mortality in patients with acute pancreatitis (AP) and sepsis remains unclear.</p> Methods <p>Data were extracted from the MIMIC-IV database for patients diagnosed with AP and sepsis. The primary research endpoints were all-cause mortality at 28, 90, and 365 days. Kaplan-Meier survival curve analysis, restricted cubic spline (RCS) receiver operating characteristic (ROC) curves, subgroup analysis, and Cox regression were employed to assess the association between RDW and mortality.</p> Results <p>A total of 759 patients with AP and sepsis were included. The all-cause mortality rates were 17.26%, 25.96%, and 31.49% at 28, 90, and 365 days, respectively. Cox regression analysis indicated that, after adjustment for covariates, elevated RDW was significantly associated with increased risk of mortality at 28, 90, and 365 days. The hazard ratios (HR) were 1.08 (95% CI: 1.02–1.14) for 28-day mortality, 1.12 (95% CI: 1.07–1.17) for 90-day mortality, and 1.13 (95% CI: 1.08–1.18) for 365-day mortality. The RCS analysis indicated a nonlinear relationship. Kaplan-Meier analysis demonstrated significantly higher mortality in the high-RDW group compared to the low-RDW group (<i>p</i> &lt; 0.001). The area under the curve (AUC) for RDW was greater than that for BISAP and SIRS, but lower than the SOFA. Subgroup analyses showed no significant interactions between RDW and most subgroups.</p> Conclusion <p>Elevated RDW is independently associated with increased short- and long-term all-cause mortality in patients with AP and sepsis.</p>