Background Acute pancreatitis (AP) is a common cause of hospitalization in the United States. Our study aimed to investigate the impact of liver cirrhosis (LC) on the outcomes of AP in adult patients hospitalized with AP. Methods We performed a retrospective study of adult patients with AP utilizing the Nationwide Inpatient Sample (NIS) database from 2020 to 2022. We compared AP outcomes in patients with and without LC. The primary outcome was all-cause inpatient mortality. Secondary outcomes were the length of stay (LOS), healthcare cost utilization adjusted to 2022, the incidence of acute renal failure (ARF), sepsis, shock, venous thromboembolism (VTE), and the need for intensive care unit (ICU) admission. Statistical analyses were performed using STATA, version 16.1 (StataCorp., College Station, Texas, USA). A multivariate logistic regression analysis was conducted to assess if gender was an independent predictor for these outcomes and to adjust for any confounders. Results From 2020 to 2022, 738,139 adult patients underwent AP admissions. Among the patients, 723,959 had AP without LC, and 14,180 had AP with LC. The mean age for patients with and without LC was the same, 50.9 years. Patients without LC had a higher prevalence of cerebrovascular accident (CVA) and obesity. Patients with LC had a higher prevalence of congestive heart failure (CHF), diabetes mellitus type 2 (DM2), diabetes mellitus type 1 (DM1), chronic kidney disease (CKD), and smoking/tobacco use. We found that AP patients with LC had a significantly higher likelihood of in-hospital mortality (aOR: 1.74, 95% CI: 1.22-2.42, P < 0.01), longer LOS (+ 0.46 days, 95% CI: 0.26-0.67, P < 0.01), higher healthcare utilization cost (+ $4163, 95% CI: $1530.9-$6796.0, P < 0.01), shock (aOR: 1.87, 95% CI: 1.42-2.46, P < 0.01), ARF (aOR: 1.44, 95% CI: 1.30-1.59, P < 0.01), ICU admission (aOR: 1.67, 95% CI: 1.38-1.91, P < 0.01), and acute VTE (aOR: 1.65, 95% CI: 1.30-2.11, P < 0.01). Conclusions We found that patients with AP who concomitantly had LC had significantly poor clinical outcomes, including higher mortality, ARF, shock, ICU admission, VTE, LOS, and total hospitalization charges as compared to AP patients who did not have LC. Our study highlights that cirrhotic patients with AP have poor inpatient hospital outcomes and need aggressive treatment to prevent morbidity and mortality.