This is a multi-center, double-blind, parallel-group, randomized, proof of concept trial to investigate the relationship between dose of esomeprazole magnesium and acid-associated heartburn symptoms during 4 weeks of treatment. The safety and tolerability of esomeprazole magnesium in doses up to 40 mg BID will also be assessed.

Inclusion Criteria:

• Males and non-lactating females, aged 18 to 75 years, inclusive, with the ability to understand English and provide written informed consent
• A history of heartburn for at least 6 months
• A history of prior positive relief of heartburn symptoms from antacids or acid suppressive therapy
• A positive esophageal acid perfusion test
• At least 3 days of 'moderate' severity heartburn over the previous 7 days
• No use of any acid suppression therapy (PPI, H2RA, etc.) within 14 days of randomization

Exclusion Criteria:

• A history of gastric or esophageal surgery
• H. pylori positive
• A history of endoscopy -verified erosive esophagitis within the 16 weeks prior to randomization
• Currently taking higher than the standard approved proton pump inhibitor doses
• Historical evidence of a number of other GI, cardiovascular, pulmonary, liver, kidney, pancreatic, cerebral vascular diseases, organ transplant, or a condition requiring surgery.