The patient reported a 869113-09-7 gastrointestinal complaint or a potential symptom that may be caused by a gastrointestinal diagnosis, or documentation of a medication where prophylaxis might be necessary. We performed a visit-level analysis using visit sampling weights to account for clustering at the physician and practice level and to generate national estimates of counts and percentages. We used the Pearson chi-squared test to compare patient and physician characteristics between 2002�C2003 and 2008�C2009. We used linear regression to test for linear trends in PPI use between 2002 and 2009 while controlling for patient and physician characteristics. We used the Pearson chi-squared test and multivariable logistic regression to test for associations between PPI use and patient, physician, and practice characteristics using data from 2008 and 2009. We also estimated the prevalence of visits in which PPIs were used by patients without gastrointestinal diagnoses, complaints, or concomitant high-risk medication use. We used multivariable logistic regression to test for associations between the patient and physician characteristics described above and PPI use in patients with no documented indication. All tests were twosided with a p-value of 0.05 considered significant. In this study of PPI use in the ambulatory setting, we found almost a three-fold increase in their use in recent years. In 2009, PPI use was documented in almost a tenth of ambulatory visits compared with close to 4 percent of visits in 2002. We explored three potential reasons for increased use of PPIs: continuation of previously prescribed PPIs, a shift to use PPIs rather than other acid reducers such as H2-blockers, and more reasons for their use because of gastrointestinal diagnoses, patient symptoms, and medications. Our finding of little change in new prescriptions for PPIs suggests that patients stay on PPIs chronically, that they may be started in settings other than the outpatient setting, or that self-prescribe 1227923-29-6 over-the-counter PPIs. The second explanation is not supported by our findings: H2-blocker use did not decrease over the study period and, in fact, increased over our study period. The third explanation, increased documented indications, may also co