The epidemiological trends contributing to increasing acute pancreatitis (AP) hospitalizations remain unknown. We sought to analyze etiological factors and outcomes of increasing AP hospitalizations. Utilizing the Nationwide Inpatient Sample, retrospective analyses of adult (≥18 years) inpatient admissions with a primary diagnosis of AP (N = 2,016,045) were performed. Patient hospitalizations from 2009 to 2012 were compared with those from 2002 to 2005. Compared with 2002-2005, there was a 13.2% (P < 0.001) increase in AP admissions in 2009-2012. Multivariate analysis adjusted for "period," patient and hospital demographics, AP etiologies, and disease associations demonstrated an increase in the odds of associated chronic pancreatitis (CP) 2002-2005: odds ratio, (OR), 32.04; 95% confidence interval (CI), 30.51-33.64; 2009-2012: OR, 35.02; 95% CI, 33.94-36.14, whereas associated odds of gallstones (2002-2005: OR, 36.37; 95% CI, 35.32-37.46; 2009-2012: OR, 29.85; 95% CI, 29.09-30.64) decreased. Compared with 2002-2005, the AP-related mortality decreased in 2009-2012 (1.62%-0.79%, P < 0.001) and was lower in AP with associated CP (0.65%-0.26%; P < 0.001) compared with AP without CP. In the preceding decade, AP hospitalizations increased, but associated mortality declined. Associated CP has emerged as a leading contributor for AP-related hospitalizations. Further research is needed to identify novel interventions to prevent disease progression of AP.