Cilostazol is a selective phosphodiesterase 3 (PDE3) inhibitor approved by the Food and Drug Administration for treatment of intermittent claudication. It has also been used in bradyarrhythmic patients to increase heart rates. Recently, cilostazol has been shown to prevent ventricular fibrillation in patients with Brugada syndrome. Cilostazol is hypothesized to suppress transient outward potassium (Ito) current and increase inward calcium current, thus, maintaining the dome (phase 2) of action potential, decreasing transmural dispersion of repolarization and preventing ventricular fibrillation. Although many PDE3 inhibitors have been shown to increase cardiac arrhythmia in heart failure, cilostazol has presented effects that are different from other PDE3 inhibitors, especially adenosine uptake inhibition. Owing to this effect, cilostazol could be an effective cardioprotective drug, with its beneficial effects in preventing arrhythmia. In this review, the cardiac electrophysiological effects of cilostazol are presented and its possible cardioprotective effects, particularly in preventing ventricular fibrillation, are discussed, with emphasis on the need to further verify its clinical benefits. © 2011 Italian Federation of Cardiology.