Esomeprazole, sold under the brand name Nexium (or Neksium) among others, is a medication which reduces stomach acid. It is used to treat gastroesophageal reflux disease, peptic ulcer disease, and Zollinger–Ellison syndrome. Its effectiveness is similar to that of other proton pump inhibitors (PPIs). It is taken by mouth or injection into a vein.

Common side effects include headache, constipation, dry mouth, and abdominal pain. Serious side effects may include angioedema, Clostridioides difficile infection, and pneumonia. Use in pregnancy appears to be safe, while safety during breastfeeding is unclear. Esomeprazole is the (S)-(−)-enantiomer (or less specifically the S-isomer) of omeprazole. It works by blocking H⁺/K⁺-ATPase in the parietal cells of the stomach.

It was patented in 1993 and approved for medical use in 2000. It is available as a generic medication and sold over the counter in several countries. In 2023, it was the 147th most commonly prescribed medication in the United States, with more than 3 million prescriptions. In Australia, it was one of the top ten most-prescribed medications between 2017 and 2023. It is also available in lower dose formulations without a prescription in the United States, the United Kingdom as well as Australia, Canada, and New Zealand.

The primary uses of esomeprazole are gastroesophageal reflux disease, treatment and maintenance of erosive esophagitis, treatment of duodenal ulcers caused by H. pylori, prevention of gastric ulcers in those on chronic NSAID therapy, and treatment of gastrointestinal ulcers associated with Crohn's disease.

Gastroesophageal reflux disease (GERD) is a condition in which the digestive acid in the stomach comes in contact with the esophagus. The irritation caused by this disorder is known as heartburn. Long-term contact between gastric acids and the esophagus can cause permanent damage to the esophagus and is associated with Barrett's esophagus. Esomeprazole reduces the production of digestive acids, thus reducing their effect on the esophagus.

Esomeprazole is combined with the antibiotics clarithromycin and amoxicillin (or metronidazole instead of amoxicillin in penicillin-hypersensitive patients) in a 10-day eradication triple therapy for Helicobacter pylori. Infection by H. pylori is a causative factor in the majority of peptic and duodenal ulcers.

A 2006 meta analysis concluded that compared to other proton pump inhibitors, esomeprazole confers a modest overall benefit in esophageal healing and symptom relief. When broken down by disease severity, the benefit of esomeprazole relative to other proton pump inhibitors was negligible in people with mild disease (number needed to treat 50^{[clarification needed]}), but appeared more in those with severe disease (number needed to treat 8^{[clarification needed]}). A second meta analysis also found increases in erosive esophageal healing (>95% healing rate) when compared to standardized doses in broadly selected patient populations. A 2017 study found esomeprazole to be among a number of effective PPIs.

Common side effects include headache, diarrhea, nausea, flatulence, decreased appetite, constipation, dry mouth, and abdominal pain. More severe side effects are severe allergic reactions, chest pain, dark urine, fast heartbeat, fever, paresthesia, persistent sore throat, severe stomach pain, unusual bruising or bleeding, unusual tiredness, and yellowing of the eyes or skin.