Abstract Background: Tigecycline, an expanded broad-spectrum glycylcycline, exhibits in vitro activity against many common pathogens associated with community-acqui red pneumonia (CAP), as well as penetration into lung tissues that suggests effectiveness in ho spitalized CAP patients. The aim of the present study was to compare the efficacy and safety of intravenous (IV) tigecycline with IV levofloxacin in hospitalized adults with CAP. Methods: In this prospective, double-blin d, non-inferiority phase 3 trial, eligible patients with a clinical diagnosis of CAP supported by radiographic evidence were stratified by Fine Pneumonia Severity Index and randomized to tigecycline or levofloxacin for 7-14 days of therapy. Co-primary efficacy endpoints were clinical response in the clinically evaluable (CE) and clinical modified intent- to-treat (c-mITT) populations at te st-of-cure (Day 10-21 post-therapy). Results: Of the 428 patients who received at least on e dose of study drug, 79% had CAP of mild-moderate severity according to their Fine score. Clinical cure rates for the CE population were 88.9% for tigecycline and 85.3% for levofloxac in. Corresponding c-mITT population rates were 83.7% and 81.5%, respectively. Eradication rates for Streptococcus pneumoniae were 92% for tigecycline and 89% for levofloxac in. Nausea, vomiting, and diarrhoea were the most frequently reported adverse events. Rates of premature disc continuation of study drug or study withdrawal because of any adverse event were similar for both study drugs. Conclusion: These findings suggest that IV tigecycline is non-inferior to IV levofloxacin and is generally well-tolerated in the treatment of hospitalized adults with CAP.