Asystole (New Latin, from Greek privative a "not, without" + systolē "contraction") is the absence of ventricular contractions in the context of a lethal heart arrhythmia (in contrast to an induced asystole on a cooled patient on a heart-lung machine and general anesthesia during surgery necessitating stopping the heart). Asystole is the most serious form of cardiac arrest and is usually irreversible. Also referred to as cardiac flatline, asystole is the state of total cessation of electrical activity from the heart, which means no tissue contraction from the heart muscle and therefore no blood flow to the rest of the body.

Asystole should not be confused with very brief pauses in the heart's electrical activity—even those that produce a temporary flatline—that can occur in certain less severe abnormal rhythms. Asystole is different from very fine occurrences of ventricular fibrillation, though both have a poor prognosis, and untreated fine VF will lead to asystole. Faulty wiring, disconnection of electrodes and leads, and power disruptions should be ruled out.

Asystolic patients (as opposed to those with a "shockable rhythm" such as coarse or fine ventricular fibrillation, or unstable ventricular tachycardia that is not producing a pulse, which can potentially be treated with defibrillation) usually present with a very poor prognosis. Asystole is found initially in only about 28% of cardiac arrest cases in hospitalized patients, but only 15% of these survive, even with the benefit of an intensive care unit, with the rate being lower (6%) for those already prescribed drugs for high blood pressure.

Asystole is treated by cardiopulmonary resuscitation (CPR) combined with an intravenous vasopressor such as epinephrine (a.k.a. adrenaline). Sometimes an underlying reversible cause can be detected and treated (the so-called "Hs and Ts", an example of which is hypokalaemia). Several interventions previously recommended—such as defibrillation (known to be ineffective on asystole, but previously performed in case the rhythm was actually very fine ventricular fibrillation) and intravenous atropine—are no longer part of the routine protocols recommended by most major international bodies. 1 mg epinephrine by IV every 3–5 minutes is given for asystole.

Survival rates in a cardiac arrest patient with asystole are much lower than a patient with a rhythm amenable to defibrillation; asystole is itself not a "shockable" rhythm. Even in those cases where an individual suffers a cardiac arrest with asystole and it is converted to a less severe shockable rhythm (ventricular fibrillation, or ventricular tachycardia), this does not necessarily improve the person's chances of survival to discharge from the hospital, though if the case was witnessed by a civilian, or better, a paramedic, who gave good CPR and cardiac drugs, this is an important confounding factor to be considered in certain select cases. Out-of-hospital survival rates (even with emergency intervention) are less than 2 percent.