The study analyzed adverse events (AEs) associated with epinephrine from US FDA reporting system data from Q1 2004 to Q4 2024 using methods such as ROR, PRR, BCPNN, and EBGM. The most frequently affected areas were general disorders and administration site reactions (n = 6,112). At the PT level, ineffective medication was most common (n = 1867), with ischemia at the injection site having the strongest signal (ROR: 3242.28; PRR: 3236.49; IC: 10.43; EBGM: 1380.84). Several new, off-label AEs showed strong signals, such as myocardial stunning, systolic anterior mitral valve motion, left ventricular outflow tract obstruction, harlequin syndrome, injection site nerve damage, and injection site motion impairment. The median time to onset of AEs was 0 days (IQR 0–0 days), with most cases occurring within 24 hours of application. The research identified numerous previously unreported AE signals and recommends further clinical studies to confirm them and clarify causality.