<b><i>Introduction:</i></b> The COVID-19 pandemic drastically changed the daily routine of all healthcare systems worldwide, and endoscopy units were no exception. Endoscopic exams were considered to have a high risk of transmission, and therefore, the safety of endoscopy units and the consequent need for pre-endoscopy SARS-CoV-2 screening were questioned early on. The aim of our study was to assess the safety of endoscopy units during the COVID-19 pandemic, as well as the effectiveness/necessity for SARS-CoV-2 screening prior to endoscopies. <b><i>Material and Methods:</i></b> This is a retrospective and single-center study carried out in a Portuguese tertiary hospital. All patients who underwent endoscopic procedures between September 1, 2020 and February 28, 2021 were included. The pre-endoscopy screening consisted of a specific questionnaire or a RT-PCR test for SARS-CoV-2 (nasal and oropharyngeal swab). Data were obtained through patient’s clinical records and the Trace COVID platform. <b><i>Results:</i></b> A total of 2,166 patients were included. Patients had a mean age of 61.8 years and were predominantly male (56.2%, <i>n</i> = 1,218). Eighty-one (3.7%) patients had previous SARS-CoV-2 infection, with a median difference of 74 days (IQ 40.5:160.5) between infection and endoscopy. Most patients (70.2%, <i>n</i> = 1,521) underwent PCR screening for SARS-CoV-2 up to 72 h before the procedure, with the remaining patients (29.8%, <i>n</i> = 645) answering a questionnaire of symptoms and risk contacts up to 3 days before endoscopy. Of the patients who underwent RT-PCR screening for SARS-CoV-2, 21 (1.4%) tested positive, and all were asymptomatic at the time of the screening. The evaluation for SARS-CoV-2 infection up to 14 days after the endoscopic exams identified 9 positive patients (0.42%) for SARS-CoV-2. The median difference in days between endoscopy and the diagnosis of infection was 10 days. <b><i>Discussion/Conclusion:</i></b> Pre-endoscopy screening with RT-PCR test for SARS-CoV-2 identified a very small number of patients with COVID-19 infection as well as patients with COVID-19 infection in the following 14 days. Therefore, the risk of infection in endoscopy units is negligible if screening of symptoms and risk contacts is applied and individual protective equipment is used.