Digoxin (better known as digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is one of the oldest medications used in the field of cardiology. It works by increasing myocardial contractility, increasing stroke volume and blood pressure, reducing heart rate, and somewhat extending the time frame of the contraction. Digoxin is taken by mouth or by injection into a vein. Digoxin has a half life of approximately 36 hours given at average doses in patients with normal renal function. It is excreted mostly unchanged in the urine.

Common side effects include breast enlargement with other side effects generally due to an excessive dose. These side effects may include loss of appetite, nausea, trouble seeing, confusion, and an irregular heartbeat. Greater care is required in older people and those with poor kidney function. It is unclear whether use during pregnancy is safe.

Digoxin is in the cardiac glycoside family of medications. It was first isolated in 1930 from Grecian foxglove (Digitalis lanata). It is on the World Health Organization's List of Essential Medicines. In 2021, it was the 241st most commonly prescribed medication in the United States, with more than 1 million prescriptions.

The most common indications for digoxin are atrial fibrillation and atrial flutter with rapid ventricular response, especially in older or less active patients, though beta blockers and/or calcium channel blockers may be preferred in some patients, such as younger more active ones, or those without heart failure or hemodynamic instability.

Early observational studies showed an increased risk of death in patients taking digoxin, despite an attempt to allow for other risk factors for death (so-called propensity score matching). However, systematic reviews focusing on randomised controlled trials of digoxin (which ensured similarity between patients on digoxin, and those not on it) showed no difference in mortality. Evidence suggested the increased mortality in patients taking digoxin was due to their having worse heart disease than those not taking it. Cardiac arrhythmias may also occur when patients are prescribed digoxin alongside thiazides and loop diuretics.

Digitalis (i.e. extracts, including digoxin, from the plant genus Digitalis) was the first drug used to treat dropsy (swollen ankles—a symptom of heart failure) following its discovery by William Withering. Alongside diuretics, it was the mainstay of treatment for heart failure for over a century. Since the introduction of other drugs with better outcomes and fewer adverse effects, it is generally now only used where heart failure is associated with atrial fibrillation and or a rapid ventricular rate. In certain circumstances it may be used under specialist guidance in addition to, or instead of, the recommended first-line treatments of ACE inhibitor, beta blocker, mineralocorticoid antagonist, and SGLT-2 inhibitor, where they are not effective or not tolerated.

Digoxin is also used intrafetally or amniotically during abortions in the late second trimester and third trimester of pregnancy. It typically causes fetal demise (measured by cessation of cardiac activity) within hours of administration.

The occurrence of adverse drug reactions is common, owing to its narrow therapeutic index (the margin between effectiveness and toxicity). Gynaecomastia (enlargement of breast tissue) is mentioned in many textbooks as a side effect, thought to be due to the estrogen-like steroid moiety of the digoxin molecule, but when systematically sought, the evidence for this is equivocal as of 2005^[update]. The combination of increased (atrial) arrhythmogenesis and inhibited atrioventricular (AV) conduction (for example paroxysmal atrial tachycardia with AV block – so-called "PAT with block") is said to be pathognomonic (that is, diagnostic) of digoxin toxicity.