Community-acquired pneumonia (CAP) of mixed etiology has increasingly been appreciated in the literature, but its clinical significance remains unknown. The aim of this analysis was to describe the prevalence, clinical characteristics, and outcome of CAP of mixed etiology. Data were obtained from a 2-year prospective study of consecutive patients with CAP in whom an extensive microbiological workup was performed. Predefined strict criteria were used to establish the etiology. A total of 493 patients were included. A single pathogen was detected in 222 (45%) cases and two or more pathogens in 28 (5.7%) cases. Mixed infections were seen across all age groups and in patients treated both in hospital and as outpatients. The most frequent combinations of pathogens were those of a bacterium plus an "atypical" organism (28.6%) and of two bacterial organisms (28.6%). Compared with patients with monomicrobial pneumonia, patients with mixed pneumonia were more likely to have underlying conditions (64% vs. 45%, p=0.04) and dementia (25% vs. 10%, p=0.02). The incidence of a defined series of complications was higher in patients with mixed pneumonia (39.3% vs. 18.6%; OR=2.84; p=0.02). Community-acquired pneumonia of mixed etiology is uncommon. Patients with mixed pneumonia are more likely to have underlying medical conditions, and they may have a more severe course of disease.