BACKGROUND: Successful therapy for community-acquired pneumonia (CAP) requires appropriate empirical antimicrobial therapy based on the local microbe and resistance patterns. However, the available data on the bacterial etiology and antimicrobial susceptibility of CAP in Korea is very limited. MATERIALS AND METHODS: A nationwide prospective multicenter study of CAP in adult patients was carried out between March 2009 and February 2010. Most patients underwent detailed assessment for bacterial and viral pathogens (cultures, urinary antigen testing, serological methods and polymerase chain reaction). RESULTS: A total of 619 patients were studied. More than half (50.4%) of the patients were > or =65 years, 59.3% were males and 48.1% had underlying illness. The etiology was identified in 246 (39.7%) of the patients. The most common etiologic agent was Streptococcus pneumoniae (52 episodes, 21.1%), and the majority (36/52) of which were diagnosed by a positive urinary antigen test alone. The other common bacterial agents included Mycoplasma pneumoniae (41, 16.7%), Klebsiella pneumoniae (26, 10.6%), Chlamydia pneumoniae (13, 5.3%), Pseudomonas aeruginosa (11, 4.3%) and Staphylococcus aureus (8, 3.1%). All S. pneumoniae isolates were susceptible to penicillin with MIC of 2 microg/mL or less, only 1/16 (6.2%) was resistant to levofloxacin and 10/16 (62.5%) were resistant to erythromycin. Of the 26 K. pneumoniae isolates, 25 (96.2%) were susceptible to cefotaxime and ciprofloxacin. CONCLUSIONS: S. pneumoniae remains the most frequent pathogen in adults with CAP and this should be covered with empirical antimicrobial treatment. Atypical pathogens such as M. pneumoniae and C. pneumoniae were the second most common etiologic agents and they should be tested for. The rate of CAP caused by gram-negative bacilli such as K. pneumoniae and P. aeruginosa was high, which is similar to that of the previous Korean studies. Further study, with excluding healthcare-associated pneumonia, is needed to clarify the etiology of CAP in Korea.