e19515 Background: Proteasome inhibitors (PI) are a class of drugs that are used in the treatment of Multiple Myeloma. There are currently three PIs (Bortezomib, Carfilzomib, and Ixazomib) approved by FDA for this indication. Peripheral neuropathy has been described as one of their most common side effects but the association with another life-threatening neurological disorder, Posterior Reversible Encephalopathy Syndrome (PRES), remains poorly understood. Methods: We conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System database to analyze the risk of PRES associated with various Proteasome Inhibitors. We employed disproportionality signal analysis and calculated the reporting odds ratio with a 95% confidence interval. Results: A total of 79,450 adverse events were found within the FAERS database that were associated with the three FDA approved PIs. PRES accounted for 274 cases, of which 165 cases were in females and 71 cases in males. Majority of patients were adults, with 119 cases between 18-64 years of age, 88 cases above 65 years, and 50 cases with age not specified. Death was reported in 70 cases while 74 cases were marked as having life threatening illness, and 152 cases needed hospitalization. Bortezomib accounted for most cases (202 cases, ROR 6.03, 95% CI 5.3-7.1), followed by Carfilzomib (68 cases, ROR 7.2, 95% CI 5.7-9.1), and Ixazomib (9 cases, ROR 0.99, 95% CI 0.5-1.7). Conclusions: The study helps to shed light on the incidence, and hospital outcomes of PRES associated with various proteasome inhibitors. Significant safety signals were found for Bortezomib, and Carfilzomib. Females were almost 2.5 times more likely to develop PRES compared to males. These findings highlight the importance of keeping a high index of suspicion for PRES while evaluating patients on PIs who present with concerning neurological symptoms.