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BACKGROUNDPost-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is new onset acute pancreatitis after ERCP. This complication is sometimes fatal. As such, PEP should be diagnosed early so that therapeutic interventions can be carried out. Serum lipase (s-Lip) is useful for diagnosing acute pancreatitis. However, its usefulness for diagnosing PEP has not been sufficiently investigated.AIMThis study aimed to retrospectively examine the usefulness of s-Lip for the early diagnosis of PEP.METHODSWe retrospectively examined 4192 patients who underwent ERCP at our two hospitals over the last 5 years. The primary outcomes were a comparison of the areas under the receiver operating characteristic (ROC) curves (AUCs) of s-Lip and serum amylase (s-Amy), s-Lip and s-Amy cutoff values based on the presence or absence of PEP in the early stage after ERCP via ROC curves, and the diagnostic properties [sensitivities, specificities, positive predictive values (PPV), and negative predictive value (NPV)] of these cutoff values for PEP diagnosis.RESULTSBased on the eligibility and exclusion criteria, 804 cases were registered. Over the entire course, PEP occurred in 78 patients (9.7%). It occurred in the early stage after ERCP in 40 patients (51.3%) and in the late stage after ERCP in 38 patients (48.7%). The AUCs were 0.908 for s-Lip [95% confidence interval (CI): 0.880-0.940, P < 0.001] and 0.880 for s-Amy (95%CI: 0.846-0.915, P < 0.001), indicating both are useful for early diagnosis. By comparing the AUCs, s-Lip was found to be significantly more useful for the early diagnosis of PEP than s-Amy (P = 0.023). The optimal cutoff values calculated from the ROC curves were 342 U/L for s-Lip (sensitivity, 0.859; specificity, 0.867; PPV, 0.405; NPV, 0.981) and 171 U/L for s-Amy (sensitivity, 0.859; specificity, 0.763; PPV, 0.277; NPV, 0.979).CONCLUSIONS-Lip was significantly more useful for the early diagnosis of PEP. Measuring s-Lip after ERCP could help diagnose PEP earlier; hence, therapeutic interventions can be provided earlier.