Oxymetazoline, sold under the brand name Afrin among others, is a topical decongestant and vasoconstrictor medication. It is available over-the-counter as a nasal spray to treat nasal congestion and nosebleeds, as eye drops to treat eye redness due to minor irritation, and (in the United States) as a prescription topical cream to treat persistent facial redness due to rosacea in adults. Its effects begin within minutes and last for up to six hours. Intranasal use for longer than three to five days may cause congestion to recur or worsen, resulting in physical dependence. Fluticasone (Flonase) and other intransal glucocorticoids are known to treat oxymetazoline dependence.

Oxymetazoline is a derivative of imidazole. It was developed from xylometazoline at Merck by Wolfgang Fruhstorfer and Helmut Müller-Calgan in 1961. A direct sympathomimetic, oxymetazoline binds to and activates α₁ adrenergic receptors and α₂ adrenergic receptors, most notably. One study classified it in the following order: α(2A) > α(1A) ≥ α(2B) > α(1D) ≥ α(2C) >> α(1B), but this is not universally agreed upon.

Another study classified it with selectivity ratios in alpha 2 adrenergic receptors of 200 for a2A vs a2B, 7.1 a2A vs a2C, and 28.2 a2B vs a2C.

In 2022, it was the 305th most commonly prescribed medication in the United States, with more than 300,000 prescriptions.

Oxymetazoline is available over-the-counter as a topical decongestant in the form of oxymetazoline hydrochloride in nasal sprays.

Due to its vasoconstricting properties, oxymetazoline is also used to treat nose bleeds and eye redness due to minor irritation (marketed as Visine L.R. in the form of eye drops).^{[citation needed]}

In the United States, oxymetazoline 1% cream was approved by the Food and Drug Administration (FDA) in January 2017 for topical treatment of persistent facial erythema (redness) associated with rosacea in adults.

In July 2020, oxymetazoline received approval by the FDA for the treatment of acquired blepharoptosis (drooping eyelid).