Background and Objectives: This study aimed to assess the impact of coronavirus disease 2019 (COVID-19) on patients with acute cholangitis (AC) by comparing outcomes, complications, and hospital stays in a tertiary Gastroenterology department. Materials and Methods: This retrospective observational cohort study was conducted in a tertiary gastroenterology department, collecting data from all AC and AC + COVID-19 patients between April 2020 and February 2022. Data included clinical and demographic information, COVID-19-specific details, acute cholangitis presentation, medical records, laboratory results, and interventions. AC was diagnosed using Tokyo Guidelines 2018 (TG18) criteria, with all patients undergoing bile culture sampling. Results: The study included 241 patients, 30 in the COVID group and 211 in the non-COVID group. The COVID group's mean age was significantly higher (74.3 vs. 67.3 years, p < 0.009). Abdominal pain was more common in the COVID group (90% vs. 70.6%, p < 0.025). Length of hospital stay was longer for COVID patients (13.5 vs. 7.9 days, p < 0.001). COVID patients had higher incidences of malignant causes of AC, with pancreatic cancer being the most common (30%). Pseudomonas spp. was significantly more prevalent in COVID patients (16.7% vs. 5.7%, p = 0.028). Conclusions: Our study results show that COVID-19 affected the duration of hospitalization for patients with AC. Furthermore, this study presents observations regarding the impact of COVID-19 on AC, revealing differences in microbial profiles.