Heart rhythm disorders, known as arrhythmias, cause significant morbidity and are one of the leading causes of mortality. Cardiac arrhythmias are frequently treated by implantable devices, such as pacemakers and defibrillators, or by ablation therapy guided by electroanatomical mapping. Both implantable and ablation therapies require sophisticated biointerfaces for electrophysiological measurements of electrograms and delivery of therapeutic stimulation or ablation energy. In this work, a graphene biointerface for in vivo cardiac electrophysiology is reported for the first time. Leveraging sub-micrometer-thick tissue-conformable graphene arrays, sensing and stimulation of the open mammalian heart are demonstrated both in vitro and in vivo. Furthermore, the graphene biointerface treatment of atrioventricular block (the kind of arrhythmia where the electrical conduction from the atria to the ventricles is interrupted) is demonstrated. The graphene arrays show effective electrochemical properties, namely interface impedance down to 40 Ω cm(2) at 1 kHz, charge storage capacity up to 63.7 mC cm(-2) , and charge injection capacity up to 704 µC cm(-2) . Transparency of the graphene structures allows for simultaneous optical mapping of cardiac action potentials, calcium transients, and optogenetic stimulation while performing electrical measurements and stimulation. The report presents evidence of the significant potential of graphene biointerfaces for advanced cardiac electrophysiology and arrhythmia therapy.