Background: A cohort of patients with bacteremic Streptococcus pneumoniae pneumonia was reviewed to assess why mortality is higher in health-care- associated pneumonia (HCAP) than in community-acquired pneumonia (CAP). Methods: A prospective cohort of all adult patients with bacteremic pneumococcal pneumonia attended at the ED was used. Results: One hundred eighty-four cases were classified as CAP and 44 (19%) as HCAP. Fifty-two (23%) were admitted to the ICU. Three (1.5%) isolates were resistant to β-lactams, and only two patients received inappropriate therapy. The CAP cohort was significantly younger (median age 68 years, interquartile range [IQR] 42-78 vs 77 years, IQR 67-82, P<.001). The HCAP cohort presented a higher Charlson index (2.81 ± 1.9 vs 1.23 ± 1.42, P<.001) and had higher severity of illness at admission (altered mental status, respiratory rate > 30/min, Pao2 /FIo2 <250, and multi-lobar involvement). HCAP patients had a lower rate of ICU admission (11.3% vs 25.5%, P<.05), and a trend toward lower mechanical ventilation (9% vs 19%, P=.17) and vasopressor use (9% vs 18.4%, P=.17) were documented. More patients in the HCAP cohort presented with a pneumonia severity index score >90 (class IV-V, 95% vs 65%, P<.001), and 30-day mortality was significantly higher (29.5% vs 7.6%, P<.001). A multivariable regression logistic analysis adjusting for underlying conditions and variables related to severity of illness confirmed that HCAP is an independent variable associated with increased mortality (odds ratio = 5.56; 95% CI, 1.86-16.5). Conclusions: Pneumococcal HCAP presents excess mortality, which is independent of bacterial susceptibility. Differences in outcomes were probably due to differences in age, comorbidities, and criteria for ICU admission rather than to therapeutic decisions. © 2010 American College of Chest Physicians. Reproduction.