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Introduction: While evidence supports shorter antibiotic courses for ventilator-associated pneumonia (VAP), limited data exist on optimal treatment durations for hospital-acquired pneumonia (HAP) in non-ventilated intensive care unit (ICU) patients. This study compares the effectiveness and safety of short-course (≤8 days) versus extended-course (9–15 days) antibiotic therapy for HAP in adult ICU patients. Methods: This retrospective, non-inferiority study included adult ICU patients treated for HAP across a multi-hospital health system from August 2022 to November 2024. Eligible patients had HAP diagnosed ≥48 hours post-admission and were treated with antibiotics. Patients were stratified into short- or extended-course therapy groups. The primary outcome was 30-day pneumonia recurrence. Secondary outcomes included 30-day mortality, ICU and hospital length of stay. A 12% non-inferiority margin was applied. Results: Of 1,420 patients screened, 180 met inclusion (93 short-course; 87 extended-course). Median APACHE II scores were similar (15 vs 16). Pneumonia recurred in 9.2% of short-course and 10.8% of extended-course patients (risk difference −1.6%, 95% CI: −10.3 to 7.2), meeting non-inferiority. Hospital stay was shorter in the short-course group (9 vs 13 days, p = 0.04). Intensive care unit stay (7 vs 8 days, p = 0.24) and 30-day mortality (10.8% vs 9.2%, p = 0.73) were similar. Pathogens were isolated in 14% of short-course and 33% of extended-course patients. Identical organisms were found in 20% in the short-course vs 100% of the extended-course patients with recurrent cultures (p = 0.04). Conclusions: Short-course therapy for HAP in ICU patients was non-inferior to extended therapy and associated with shorter hospitalization, adding to evidence supporting shorter durations in HAP and aligning with stewardship goals.