Background: We compared the in vitro activities of tigecycline with those of other agents against 97 Streptococcus pneumoniae, 140 Haemophilus influenzae and54 Moraxella catarrhalis strains isolated in two large university hospitals in Istanbul. Methods: For analysis, the agar dilution method was used. Results: For S. pneumoniae isolates, 32% were not susceptible to penicillin (28.9% intermediate and 3.1% resistant). Cefotaxime, telithromycin, moxifloxacin and linezolid were fully active. Tigecycline had a 90% minimum inhibitory concentration (MIC₉₀) of 0.12 μg/ml. For H. influenzae, 8.57% were not susceptible to ampicillin, among which 8 possessed β-lactamase (5.7%). Four (2.87%) H. influenzae isolates with β-lactamase-negative and ampicillin-resistant phenotype were found. All isolates were susceptible to ceftriaxone, azithromycin, ciprofloxacin, levofloxacin and moxifloxacin. MIC₉₀ for tigecycline was 0.5 μg/ml. Of 54 M. catarrhalis isolates, 88.9% possessed β-lactamase. Tigecycline and fluoroquinolones were highly active (MIC₉₀ ≤0.12 μg/ml). Conclusions: Linezolid, telithromycin, newer fluoroquinolones and tigecycline all have excellent in vitro activities against the 3 respiratory pathogens.