It is unclear whether prolonged motility monitoring improves the diagnostic yield of standard esophageal tests in patients with noncardiac chest pain. Our aim was to assess the diagnostic value of ambulatory 24-hr pH and pressure monitoring in patients with noncardiac chest pain. Stationary manometry, edrophonium testing, and ambulatory pH and motility studies were performed in 90 consecutive patients with recurrent chest pain and normal coronary angiograms. Normality limits of ambulatory 24-hr motility were established in 30 healthy controls. The diagnoses of specific esophageal motility disorders (nutcracker esophagus and diffuse esophageal spasm) by stationary and ambulatory manometry were discordant in 48% of the patients. Edrophonium testing was positive in 9 patients, but correlated poorly with esophageal diagnoses. During ambulatory studies, 144 chest pain events occurred in 42 patients, and 72 (50%) were related to esophageal dysfunction. Strict temporal associations of events with esophageal dysfunction in relation to ambulatory 24-hr pH/motility scores permitted four patient categorizations: true positives (event-related and abnormal tests), N = 15; true negatives (event-unrelated and abnormal tests), N = 10; reduced esophageal pain threshold (event-related and normal tests), N = 4; and indeterminate origin (event-unrelated and normal tests), N = 13. Overall, 19 patients (21%) had a probable esophageal cause for chest pain (14 esophageal motility disorder, 4 acid reflux, 1 both). In conclusion, ambulatory manometry increases the diagnostic yield of standard esophageal testing in noncardiac chest pain, but the gain is small. Causes of chest pain other than high esophageal pressures and acid reflux must still be sought in most patients with chest pain of unknown origin after a negative cardiac work-up.