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Background: The outbreak of the coronavirus disease 2019 (COVID-19) has led to significant changes in endoscopy units worldwide, with potential impact on patients’ welfare as well as on endoscopy training. We aimed to assess the real-life impact of COVID-19 on the endoscopy unit in a tertiary care center from Romania. Methods: A 6.5-month period during the COVID-19 pandemic was compared to a similar period from 2019. Results: A 6.2-fold decrease of endoscopic procedures was noted. Colonoscopies were reduced from 916 to 42, <i>p</i> < 0.001; flexible sigmoidoscopies from 189 to 14, <i>p</i> = 0.009; upper gastrointestinal (GI) endoscopies from 2269 to 401, <i>p</i> = 0.006; and ERCP from 234 to 125, <i>p</i> < 0.001. The percentage of emergency procedures increased (38.8% vs. 26.2%, <i>p</i> < 0.001), as well as the rate of endoscopies performed for upper GI bleeding (42.5% vs. 24.4%, respectively, <i>p</i> < 0.001). The detection of cancers was considerably reduced (57 compared to 249, <i>p</i> = 0.001). There were fewer complications and higher success rates (7.6% vs. 19.2%, <i>p</i> < 0.001, and 94.2% vs. 90.7%, respectively). Fellows participation was also reduced from 90% to 40.9% (<i>p</i> < 0.001). Conclusions: The COVID-19 pandemic has significantly altered the workflow of the endoscopy unit, lowering the number of procedures performed and potentially compromising the early detection of cancers.