An H₂ antagonist is a drug used to block the action of histamine on parietal cells in the stomach, decreasing acid production by these cells. They are used in the treatment of peptic ulcers.

H₂ antagonist drugs (such as cimetidine) work by blocking the H₂ subtype of histamine receptors. These are different receptors from those involved in the allergic response.

Since the advent of proton pump inhibitors, use of these drugs to treat ulcers has declined.