AIMS: This study aimed to provide a credible and comprehensive safety assessment on panoramic adverse events (AEs) associated with onasemnogene abeparvovec (OA) therapy. METHODS: Disproportionality analysis was conducted, using reporting odds ratio (ROR) method in tandem with Bayesian confidence propagation neural network (BCPNN). Two-sample Kolmogorov–Smirnov test was applied to analyze the distribution time-to-onset (TTO) of adverse events as TTO algorithm to determine pharmacovigilance signals which were inconclusive by BCPNN. Omega shrinkage was conducted to investigate drug-drug interaction between OA and its concomitant drugs. Multi-factor regression was conducted to evaluate association between OA-induced adverse events and outcomes of the reports. RESULTS: In total, 1,033 cases of OA treated patients were included for the study, and 124 pharmacovigilance signals were confirmed by ROR in tandem with BPCNN, most of which were previously unrecorded by the package-insert. Meanwhile, there were 13 signals including cardiac arrest, multiple organ dysfunction syndrome and signals referring to respiratory disorders, were determined by ROR in tandem with the TTO algorithm. Four symptoms including cyanosis, cardiac arrest, hypoxia and respiratory failure, needed to be closely monitored, due to the association with mortal outcomes. CONCLUSIONS: This study might enhance the understanding of safety profile of OA Healthcare providers should be vigilant about severe adverse reactions when administrating OA.