Bilirubin (BIL) and creatinine (Cr) have been used as potential early predictors of the severity of many diseases. A recent study found that the Cr to BIL ratio (CTR) was more sensitive and specific than either serum Cr or BIL alone. Our research focused on the clinical significance of CTR in evaluating the severity and prognosticating outcomes of acute pancreatitis (AP) in patients. Patients diagnosed with AP at the First Affiliated Hospital of Guangdong Pharmaceutical University between July 1, 2016, and December 31, 2020 were included. The analysis then focused on examining the relationship between CTR levels and the severity of the illness, the occurrence of complications, and the prognosticating outcomes for individuals diagnosed with AP. A total of 286 AP patients were enrolled. Multivariate regression analyses showed that patients with AP with increased CTR levels had a poorer disease (easier to develop severe AP); higher Ranson, and Acute Physiology and Chronic Health Evaluation (APACHE-II) scores; higher incidence of organ failure (acute heart failure, acute kidney injury and acute myocardial infarction ); and leading to a worse prognosis characterized more by frequent use of vasoactive and diuretic agents. When CTR >14.05, AP patients had increased occurrence of AHF and AKI, higher 30-day all-cause mortality rates, more frequently using vasoactive agent and diuretic agent. Besides, the disease severity scores and hospital stays were markedly increased. Patients with AP who exhibit higher CTR levels tend to experience escalating disease severity, more complications, and a poorer outcome compared with those with lower CTR levels.