A retrospective cohort study evaluated the effectiveness and risks of antibiotic therapy with limited anaerobic coverage (LAC) versus extended anaerobic coverage (EAC) in patients admitted for community-acquired aspiration pneumonia. The study included 3,999 patients across 18 hospitals in Ontario, Canada, from 2015 to 2022. Patients were categorized into LAC or EAC groups based on their initial antibiotic regimen. The primary outcome was in-hospital mortality, while secondary outcomes included the risk of Clostridioides difficile colitis. The study found no significant difference in in-hospital mortality between the LAC and EAC groups, with adjusted risk differences of 1.6% (95% CI, -1.7% to 4.9%) for mortality and 1.0% (95% CI, 0.3%-1.7%) for C difficile colitis. These results suggest that extended anaerobic coverage does not provide additional mortality benefits and may increase the risk of C difficile colitis. The study supports the 2019 American Thoracic Society and Infectious Diseases Society of America guidelines, which recommend against routine addition of anaerobic coverage for aspiration pneumonia due to potential harms. The study highlights the importance of avoiding unnecessary antibiotic use to reduce the risk of antibiotic resistance and adverse effects like C difficile colitis. It also emphasizes the need for targeted antibiotic therapy in aspiration pneumonia, using first-line antibiotics such as ceftriaxone or levofloxacin without additional anaerobic coverage. The findings contribute to real-world clinical evidence supporting the guidelines and underscore the importance of antimicrobial stewardship in hospitals.A retrospective cohort study evaluated the effectiveness and risks of antibiotic therapy with limited anaerobic coverage (LAC) versus extended anaerobic coverage (EAC) in patients admitted for community-acquired aspiration pneumonia. The study included 3,999 patients across 18 hospitals in Ontario, Canada, from 2015 to 2022. Patients were categorized into LAC or EAC groups based on their initial antibiotic regimen. The primary outcome was in-hospital mortality, while secondary outcomes included the risk of Clostridioides difficile colitis. The study found no significant difference in in-hospital mortality between the LAC and EAC groups, with adjusted risk differences of 1.6% (95% CI, -1.7% to 4.9%) for mortality and 1.0% (95% CI, 0.3%-1.7%) for C difficile colitis. These results suggest that extended anaerobic coverage does not provide additional mortality benefits and may increase the risk of C difficile colitis. The study supports the 2019 American Thoracic Society and Infectious Diseases Society of America guidelines, which recommend against routine addition of anaerobic coverage for aspiration pneumonia due to potential harms. The study highlights the importance of avoiding unnecessary antibiotic use to reduce the risk of antibiotic resistance and adverse effects like C difficile colitis. It also emphasizes the need for targeted antibiotic therapy in aspiration pneumonia, using first-line antibiotics such as ceftriaxone or levofloxacin without additional anaerobic coverage. The findings contribute to real-world clinical evidence supporting the guidelines and underscore the importance of antimicrobial stewardship in hospitals.