The purpose of this study is to confirm and complement previous data regarding an association between gastroesophageal reflux disease and appendectomy.The Korean National Health Insurance Service-National Sample Cohort includes data from people ≥ 20 years old collected from 2002 to 2013. A total of 13,484 participants who received an appendectomy were matched with 53,936 controls at a 1:4 ratio. We analyzed the previous histories of gastroesophageal reflux disease (GERD) in the appendectomy and control groups. Appendectomies were identified using operation codes (Q2860-Q2863) exclusive for appendicitis (International Classification of Disease-10 (ICD-10): K35). GERD was defined using the ICD-10 (K21), and patients who were treated ≥ 2 times and were prescribed a proton pump inhibitor (PPI) for ≥ 2 weeks were included. Crude (simple) and adjusted odds ratios (ORs) for GERD and appendectomy were analyzed using conditional logistic regression analyses.A higher GERD rate was detected in the appendectomy group (11.4% [1,713/15,062]) than in the control group (8.2% [4,947/60,248], P < .001). Adjusted ORs for GERD were 1.37 (95% confidence interval [CI] = 1.30-1.45) (P < .001). Subgroup analyses stratified according to age and sex revealed consistent findings. The adjusted OR for GERD in participants prescribed PPIs for ≥ 30 days was 1.31 (95% CI = 1.20-1.43), and the adjusted OR for GERD in participants prescribed PPIs for ≥ 60 days was 1.30 (95% CI = 1.15-1.48).The Odds for GERD were higher in the appendectomy group than in the control group.