Comorbidities, age, severity of illness, and high risk pathogens are well-known outcome determinants in community-acquired pneumonia (CAP). How these factors interact has not yet been clarified. We conducted this study to analyze the complex interaction of comorbidities, age, illness severity, and pathogens in relation to CAP. We performed a secondary analysis of the Community-Acquired Pneumonia Organization database to evaluate the impact of age in different age groups (<65, 65-79, and ≥80 yr), comorbidities (malignant disease, chronic obstructive pulmonary disease, renal and liver disease, cerebrovascular accident, congestive heart failure, and diabetes mellitus), severity of illness at admission, and etiology on the mortality of patients admitted to the hospital with CAP. A total of 6,205 patients met the inclusion criteria, and 508 (8.2%) died within 30 days. Factors independently associated with mortality were malignant disease, congestive heart failure, cerebrovascular accident, renal disease, diabetes mellitus, altered mental status, hypoxemia, pleural effusion, hematocrit less than 30%, requirement for mechanical ventilation, and being age 80 years and older. A total of 1,699 pathogens were defined in 1,545 cases; the etiology was the same for all age groups. In the overall population, mortality increased with age, but etiology was not associated with mortality. When we analyzed the patients with one comorbidity or less, we found that mortality was not different between patients younger than 65 old and those 65-79 years old, but it was higher for those aged 80 years and older. The presence of comorbidities is associated with poorer outcomes in CAP. However, when one comorbidity or less was present, we found that being age 80 years or older was a factor that increased mortality. From a clinical standpoint, this study suggests that being age 80 years or older, instead of age 65 years and older, should be considered a risk factor for poor outcome in CAP.