The intravenous (IV) formulation of esomeprazole, the S-isomer of the proton pump inhibitor (PPI) omeprazole, is currently under FDA review for the short-term treatment of gastroesophageal reflux disease (GERD) as an alternative in patients unable to continue taking oral esomeprazole. Clinical studies have shown esomeprazole to be equivalent to the other currently available PPIs with respect to safety. The intravenous formulation, given either as a 30-minute infusion or 3-minute injection, has been found to be comparable to the oral dosage form based on pharmacokinetic and pharmacodynamic studies in healthy subjects. Limited studies suggest that IV esomeprazole 40 mg/d may provide a more effective antisecretory profile than either IV lansoprazole 30 mg/d or IV pantoprazole 40 mg/d. Data on clinical efficacy is limited to 1 abstract that reported no significant differences in healing rates in subjects with erosive esophagitis administered esomeprazole either 40 mg orally or IV daily. More clinical studies are needed to define its limited role as an alternative in those patients with acid-related disorders unable to tolerate the oral formulations.