Background and Aims Gastrointestinal (GI) endoscopy is a limited health resource because of a scarcity of qualified personnel and limited availability of equipment. Non-adherence to endoscopy appointments therefore wastes healthcare resources and may compromise the early detection and treatment of GI diseases. We aimed to identify factors affecting non-attendance at scheduled appointments for GI endoscopy and thus improve GI healthcare outcomes. Methods This was a single-center retrospective cohort study performed at a tertiary hospital gastroenterology endoscopy unit, 12 months before and 12 months after the start of the COVID-19 pandemic. We used multiple logistic regression analysis to identify variables associated with non-attendance at scheduled appointments. Results Overall, 5,938 appointments were analyzed, and the non-attendance rate was 18.3% (1,088). The non-attendance rate fell significantly during the pandemic (22.6% vs. 11.6%, p < 0.001). Multivariable regression analysis identified the absence of deep sedation (OR: 3.253, 95% CI [2.386–4.435]; p < 0.001), a referral from a physician other than a gastroenterologist (OR: 1.891, 95% CI [1.630–2.193]; p < 0.001), a longer lead time (OR: 1.006, 95% CI [1.004–1.008]; p < 0.001), and female gender (OR: 1.187, 95% CI [1.033–1.363]; p = 0.015) as associated with appointment non-attendance. Conclusions Female patients, those undergoing endoscopic procedures without deep sedation, those referred by physicians other than gastroenterologists, and with longer lead time were less likely to adhere to appointments. Precautions should be directed at patients with one or more of these risk factors, and for those scheduled for screening procedures during the COVID-19 pandemic.