Backgrounds Acute pancreatitis (AP) has been reported in patients treated with protease inhibitors (PIs), but there are few real-world studies comparing the occurrence and characteristics of AP after different PI regimens. Research design and methods Disproportionality analysis and Bayesian analysis were utilized for data mining of the Food and Drug Administration's Adverse Event Reporting System (FAERS) database for suspected adverse events involving AP after PI. The times to onset and fatality rates of AP following different PI regimens were also compared. Results Based on 33,832 reports related to PIs, 285 cases were associated with AP, involving with 12 out of the 15 studied PIs. Of all the reported AP events related to PIs, 64.56% occurred in men and the median time to onset of AP was 103 (IQR: 26-408) days after the initiation of PI treatment with a fatality rate of 14.02%. Among all PI therapies, indinavir was notably associated with AP, and ritonavir and lopinavir/ritonavir-induced AP cases appeared to be associated with a higher risk of death. Conclusions Most of PIs were associated with AP-related adverse events, among which indinavir has a stronger association with AP but there is no significant difference in fatality rates.