Purpose To evaluate the effects of somatostatin analogs and disease activity status on the upper gastrointestinal system in patients with acromegaly. Methods One hundred eighty-one patients with acromegaly were retrospectively assessed. The demographic, biochemical, pathologic, and radiologic data of the patients were evaluated. The upper gastrointestinal endoscopies and endoscopic biopsies were investigated. We divided patients into four groups according to the use of somatostatin analogs, and into two groups according to disease activity. We compared the data of patients between groups A, B, C, and D, and controlled/uncontrolled groups separately. Results Before and in the peri-endoscopic period, 67 and 27 patients were being treated with octreotide long-acting release (LAR) (group A) and lanreotide autogel (group B), respectively. Twenty-one patients used somatostatin analogs, but they were stopped for various reasons before upper gastrointestinal endoscopy (group C), and 66 patients did not use a somatostatin analog (group D). In the peri-endoscopic period, 103 (60%) patients were responsive to medical and/or surgical treatment and 67 (40%) patients were non-responsive. The rate of gastritis was higher in group A than in groups B and D. The incidence of duodenitis and gastric ulcer was much higher in group D. The rate of gastritis was higher in the controlled group compared to the uncontrolled group. Conclusion The study showed that octreotide LAR treatment could be a risk factor in addition to known factors for the development of gastritis in patients with acromegaly.