Wireless pH studies are widely used to assess the presence and severity of gastroesophageal reflux disease. We hypothesized that sedation or air insufflation during a preceding endoscopy may systematically alter results. A retrospective review of ambulatory pH studies completed between January 2008 and April 2010 was performed. The pH capsule was placed 6 cm above the endoscopically determined location of the squamocolumnar junction or 5 cm above the manometrically localized upper border of the lower esophageal sphincter (LES). A total of 356 patients (65% women) underwent pH studies using the BRAVO system (GIVEN Imaging, Yoqneam, Israel). In 186 patients (E-P), the capsule was placed during endoscopy. In 170 patients (M-P), capsule placement was based on manometric determination of LES boundaries using pharyngeal anesthesia only. Endoscopic placement was successful in all cases, whereas two patients could not tolerate capsule insertion with topical anesthesia only. The mean recording time did not differ between the two groups (E-P: 2468 ± 38 min; M-P: 2415 ± 40 min). The number of patients with abnormal findings on day 1 but normal results for day 2 was similar with 15% for E-P compared with 11% for M-P. However, there was a significant difference in total acid exposure times between days 1 and 2 for endoscopically (day 1: 7.3 ± 1.2; day 2: 4.8 ± 0.5; P < 0.01), but not manometrically based placement (day 1: 7.7 ± 0.7; day 2: 7.2 ± 0.6). There was no difference in the number of symptoms between days or groups (E-P day 1:13.4 ± 1.3; E-P day 2: 16.0 ± 1.6; M-P day 1: 14.1 ± 2.1; M-P day 2: 15.7 ± 2.0). Similarly, the symptom sensitivity index did not differ significantly between days and groups (E-P: day 1: 4.1 ± 0.5; day 2: 5.9 ± 0.8; M-P: day 5.3 ± 0.8; day 2: 5.7 ± 0.8). The majority of patients tolerate insertion of a wireless pH monitoring capsule without sedation. Unsedated placement did not negatively affect total recording times. Although endoscopy resulted in higher acid exposure on day one it did not significantly increase the overall fraction of abnormal tests. If confirmed in prospective studies, the more consistent findings and a potential to lower cost favor manometrically guided capsule placement.