ABSTRACT Background Sugammadex is a novel agent that reverses neuromuscular blockade during general anesthesia. Recent case reports have raised concerns regarding potential cardiac adverse events (CAEs). However, no large-scale real-world studies have yet evaluated the potential link between sugammadex and CAEs. Research design and methods Data from the FDA Adverse Event Reporting System were obtained. The association between sugammadex and CAE was evaluated using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods. Serious outcomes resulting from sugammadex-related CAEs were assessed, and complications associated with CAEs were evaluated. Results Nineteen CAEs were identified and classified into two categories: cardiac arrhythmias and coronary artery disorders. The most frequent CAEs were bradycardia (n = 202), cardiac arrest (n = 119), tachycardia (n = 30), and Kounis syndrome (n = 22). Subgroup analysis based on age, sex, and weight revealed parallel findings. The CAEs most likely to result in serious consequences were pulseless electrical activity and cardiac arrest. The most common concurrent adverse effects with CAEs were hypotension (n = 51), anaphylactic reactions (n = 46), and anaphylactic shock (n = 23). Conclusion This study suggests a potential link between sugammadex and CAEs, highlighting the need for careful monitoring and personalized risk assessment, especially in patients with cardiovascular risk factors.