Background: Acute pancreatitis is an emergency gastrointestinal condition for which severity prediction is crucial during hospitalization. This study aimed to compare the diagnostic accuracy of inflammatory markers with gold standard scoring systems in predicting pancreatitis severity.Materials and methods: A prospective, hospital-based, cohort study was conducted, including 249 patients diagnosed with acute pancreatitis via clinical examination. Laboratory investigations and radiological investigations were conducted. The diagnostic accuracy of the inflammatory markers neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), red cell distribution width (RDW), and prognostic nutritional index (PNI) was compared with gold standard prognostic scores, namely, the Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), Bedside Index of Severity in Acute Pancreatitis (BISAP), and Systemic Inflammatory Response Syndrome (SIRS), in predicting primary and secondary outcomes. All values were analyzed using mean and standard deviation (SD). Sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve for mortality prediction were calculated for NLR, LMR, RDW, and PNI.Results: Of 249 patients with acute pancreatitis (mean age: 39-43 years), 94 were classified as mild acute, 74 as moderately severe acute, and 81 as severe acute. The most common etiology was alcohol use (40.2%), followed by gallstones (29.7%), hypertriglyceridemia (6.4%), steroid use (4%), diabetic ketoacidosis (2.8%), hypercalcemia (2.8%), and complication of endoscopic retrograde cholangiopancreatography (2%). On day 1, mean values of NLR, LMR, RDW, and PNI were 8.23±5.11, 2.63±1.76, 15.93±3.64, and 32.84±8.13, respectively. Compared to APACHE II, SAPS II, BISAP, and SIRS on day 1, day 3, day 7, and day 14, the cutoff values for NLR were 4.06, 10.75, 8.75, and 13.75, respectively. Similarly, on day 1, the cutoff value of LMR was 1.95, and on day 1 and day 3, the cutoff values of RDW were 14.75% and 15%, respectively.Conclusion: The results indicate that inflammatory biomarkers NLR, LMR, RDW, and PNI are comparable with gold standard scoring systems for predicting the severity and mortality of acute pancreatitis. NLR on day 7 was significantly associated with higher severity of illness. NLR on days 3, 7, and 14, LMR on day 1, and RDW on days 1 and 3 were significantly associated with mortality.