OBJECTIVE: To examine antibiotic prescribing and outcomes in outpatient treatment of community-acquired pneumonia in non-elderly adults. METHODS: We analyzed claims from eight managed care organizations. Index claims were outpatient or emergency department visits in 1999-2001 by individuals aged 25-64 with primary diagnosis of pneumonia, antibiotic prescription within three-days, chest x-ray on index date, continuous enrollment for 12-months prior, 30-days after index visit. Exclusion criteria: antibiotic prescription, pneumonia diagnosis, or hospitalization in prior 30-days; initial therapy with multiple antibiotics; in prior 12-months residence in a long-term care facility or diagnosis of cancer of bronchus or lung, secondary malignancy, HIV/AIDS, cystic fibrosis, immunity disorders. We considered the following comorbid illnesses: chronic liver, renal or lung disease; cerebrovascular disease; cardiac disease; diabetes mellitus; malignancy. RESULTS: A total of 5748 cases met criteria, 13.9% initially seen in the emergency department. Of these, 16.8% had one comorbidity, 3.5% had multiple comorbidities. Macrolides were the most common initial therapy (66.5%), followed by quinolones (17.9%). Quinolone use more than doubled from 1999 to 2001, from 11.8% to 24.3% in patients without comorbidity, from 12.1% to 33.8% in patients with comorbidities. Overall, 13.1% received a change in therapy without subsequent hospitalization, another 3.0% were hospitalized. Females were more likely to change therapy than males (15.9% vs. 10.5%, p<0.0001) but not more likely to be hospitalized (3.0% for both). Failure rates were strongly associated with number of comorbidities (p=0.0004), particularly in rates of subsequent hospitalization: 2.4% for no comorbidities, 4.9% for one comorbidity and 7.5% for multiple comorbidities. Hospitalization without secondary outpatient therapy was common: 13.5% for patients without comorbidity, 24.9% for one comorbidity, 28.6% for multiple comorbidities. CONCLUSION: While macrolides were the most common therapy, quinolone usage was substantial and rising rapidly regardless of comorbidity. Hospitalization for patients failing therapy was fairly common even in patients without comorbidity.