Background Acute on chronic pancreatitis (ACP) shares a similar clinical presentation with acute pancreatitis (AP) and is often diagnosed and treated in the same way. However, these two conditions may have distinct clinical risk profiles and prognoses. There is currently limited evidence available regarding the specific characteristics of ACP. Methods This retrospective cohort study included all adult patients admitted with a diagnosis of AP or ACP between 2017 and 2019 at two tertiary referral centers. The primary outcome was disease severity as defined by the Atlanta classification. Secondary outcomes included the presence of local and systemic complications, organ failure, ICU admission, and mortality. Differences in outcomes between ACP and AP were compared using multivariate logistic regression models, with results presented as odds ratios (ORs). Results We included 1163 patients, 90% of whom had AP and 10% had ACP. ACP patients were predominantly male (81 vs. 46%; P < 0.001), whereas AP patients were older (mean age 62.6 vs. 56.5 years, P < 0.001). ACP patients had lower amylase and lipase levels (P < 0.001). Multivariate analysis showed no difference in the risk of moderate or severe pancreatitis (OR, 1.15; 95% CI, 0.66–1.98; P = 0.615). ACP patients had a higher risk of local complications (predominantly pseudocysts) (OR, 1.71; 95% CI, 1.00–2.92; P = 0.049) and a lower risk of organ failure (P = 0.019) and ICU admission (P = 0.005). Conclusion Our study confirms previous observations that ACP has a more favorable in-hospital prognosis than AP and extends these findings to a modern European setting.