Isatuximab, a cluster of differentiation 38 (CD38)-targeting monoclonal antibody, is used to treat relapsed or refractory multiple myeloma.This study aimed to detect the safety signal of isatuximab and to compare the reporting ratio with daratumumab, another CD38-targeting monoclonal antibody.Food and Drug Administration Adverse Event Reporting System (FAERS) data from Q1 2020 to Q1 2022 were analyzed.A disproportionality analysis was performed, and adverse events (AEs) that satisfied the criteria for a safety signal were identified.The reporting odds ratio (ROR) of the safety signal was calculated for both isatuximab and daratumumab.The relative index (ROR ratio for fatigue) was compared between isatuximab and daratumumab.From 347 isatuximab-AE pairs, 14 were identified as safety signals.Three AEs (pulmonary embolism, atrial fibrillation, and tumor lysis syndrome) were not included on the drug label, although pulmonary embolism might be a complication of multiple myeloma or an AE of coadministered immunomodulatory agents instead.Squamous cell skin cancer (ROR, 84.25 vs. 6.12),pneumocystis jirovecii pneumonia (ROR, 67.78 vs. 2.94), lymphopenia (ROR, 26.66 vs. 1.96), bronchitis (ROR, 23.31 vs. 2.55), pneumonia (ROR, 19.52 vs. 3.39), pulmonary embolism (ROR, 18.22 vs. 3.97), atrial fibrillation (ROR, 12.51 vs. 3.93), and neutropenia (ROR, 4.48 vs. 1.47) were frequently reported with isatuximab.These AEs need to be considered when using isatuximab.