Although a wide variety of recognized pathogens causes community-acquired pneumonia, the precise etiology in Japan remains unknown. We prospectively investigated the etiology in 232 patients with community-acquired pneumonia who visited 20 community-general hospitals. New diagnostic methods, using polymerase chain reaction (PCR) assays and urinary antigen tests were employed, in addition to conventional methods. The frequency of identification of causative pathogens was high (73.3%), and the leading organism was Streptococcus pneumoniae (24.6%), followed by Haemophilus influenzae (18.5%), viruses (16.4%), Chlamydia pneumoniae (6.5%), Mycoplasma pneumoniae (5.2%), and Legionella spp. (3.9%). S. pneumoniae and M. pneumoniae were the most prevalent pathogens in younger patients, and S. pneumoniae and H. influenzae were the most prevalent in elderly patients. Multiple or mixed infections were found in 25.9% of all patients and in 35.3% with a causal diagnosis. The results have important practical implications for the initial treatment of adult patients with community-acquired pneumonia.