Recent studies have shown that many patients use acid suppression medications after antireflux surgery. The aim of this study was to determine the frequency of gastroesophageal reflux disease in a cohort of surgically treated patients with postoperative symptoms and a high prevalence of acid suppression medication use. The study group consisted of 86 patients who had symptoms following Nissen fundoplication that were sufficient to merit evaluation with 24-hour distal esophageal pH monitoring. All completed a detailed symptom questionnaire. The mean postoperative follow-up period was 28 months (median 18 months). Thirty-seven patients (43%) were taking acid suppression medications after fundoplication. Only 23% (20 of 86) of all the patients and only 24% (9 of 37) of those taking acid suppression medications had abnormal esophageal acid exposure on the 24-hour pH study. Heartburn and regurgitation were the only symptoms that were significantly associated with an abnormal pH study. Endoscopic assessment of the fundoplication was the most significant factor associated with an abnormal pH study. Multivariable logistic regression analysis showed that patients with a disrupted, abnormally positioned fundoplication had a 52.6 times increased risk of abnormal esophageal acid exposure. Most patients who use acid suppression medications after antireflux surgery do not have abnormal esophageal acid exposure, and the use of these medications is thus often inappropriate. Because of the limited predictive power of symptoms, objective evidence of reflux disease should be obtained before prescribing acid suppression medication for patients who have undergone antireflux surgery.