Patients undergoing lung resection may be at risk of gastroesophageal reflux (GER) and silent aspiration following surgery. Defining high-risk patients may lead to prevention strategies for silent aspiration and subsequent exacerbation of underlying pulmonary disease. A pilot study of 50 patients was performed to investigate postoperative gastroesophageal reflux disease (GERD) symptoms and the pepsin concentration in saliva. Patients answered a questionnaire concerning GERD symptoms before lung surgery and at the time of discharge. Saliva samples were obtained before surgery, on the third postoperative day and at discharge. Pepsin concentration was measured with Peptest. The pepsin concentration in saliva following resection was significantly elevated on postoperative day 3, but it returned to the baseline level at discharge. Patients undergoing resection of four or more lung subsegments had a continuously elevated pepsin concentration in saliva on postoperative day 3 [mean difference 65.63 ng/mL, 95% confidence interval (CI): 9.130-122.1] and at discharge (mean difference 76.22 ng/mL, 95% CI: 19.72-132.7). Patients with a >10% reduction of forced expiration volume in one second also had a continuous elevated pepsin concentration from the 3rd postoperative day. Lung resection resulted in elevated pepsin concentration in the saliva, which persisted in patients who received resections equivalent to or more than right middle lobectomy in volume. Resection of large volumes of lung may lead to anatomical changes and changes in breathing patterns and result in GER.