Backgrounds: The potential therapeutic effects of protease inhibitors (PIs), such as lopinavir/ritonavir and darunavir, on COVID-19 are being tested in clinical trials. Although acute pancreatitis HP pancreatitis MESHD (AP) has been reported in patients treated with PIs, there have been few real-world studies comparing the occurrence and characteristics of AP after different PI regimens. 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 from January 2004 to December 2019. 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 (0.84% of total adverse drug reactions, ADRs) were associated with AP; in these reports, the number of AP cases reported for the top five PIs was as follows: ritonavir/dasabuvir/ombitasvir/paritaprevir, 64 (22.46%); ritonavir, 54 (18.95%); atazanavir, 52 (18.25%); lopinavir/ritonavir, 48 (16.84%); and darunavir, 26 (9.12%). Twelve out of the 15 studied PIs, including lopinavir/ritonavir, darunavir and nelfinavir, which are potential therapeutics for COVID-19, were associated with AP. Of all the reported adverse events involving AP related to PIs, 64.56% occurred in men, which was a much higher proportion than what was observed in women (28.42%). The median time to onset of AP was 103 (IQR: 26-408) days after the initiation of PI treatment. Patients treated with ritonavir/dasabuvir/ombitasvir/paritaprevir appeared to have an earlier onset of AP than those receiving atazanavir (31 [IQR: 17–68.25] days vs 187.5 [IQR: 80.5–556.5] days, p=0.0379) or ritonavir (31 [IQR: 17–68.25] days vs 177 [IQR: 56–539] days, p=0.0371). Compared with AP cases induced by all studied PIs, which had a fatality rate of 14.02%, AP cases associated with ritonavir (18.87%) and lopinavir/ritonavir (22.73%) appeared to be associated with a higher risk of death MESHD. Conclusions: Analysis of the FAERS data provides a more precise understanding of the occurrence and characteristics of AP after different PI regimens. Signals for AP associated with various PI regimens have been detected. The findings support continued surveillance, risk factor identification, and comparative studies.