['We evaluated the respective influence of the causative pathogen and infection site on hospital mortality from severe sepsis related to community-, hospital-, and intensive care unit-acquired infections.', 'We used a prospective observational cohort 10-yr database. We built a subdistribution hazards model with corrections for competing risks and adjustment for potential confounders including early appropriate antimicrobial therapy.', 'Twelve intensive care units.', 'We included 4,006 first episodes of acquisition-site-specific severe sepsis in 3,588 patients. INTEVENTIONS: None.', 'We included 1562 community-acquired, 1432 hospital-acquired, and 1012 intensive care unit-acquired episodes of severe sepsis. After adjustment, we found no independent associations of the causative organism, multidrug resistance of the causative organism, infection site, or presence of bacteremia with mortality. Early appropriate antimicrobial therapy was consistently associated with better survival in the community-acquired (0.64 [0.51-0.8], p = .0001), hospital-acquired (0.72 [0.58-0.88], p = .0011), and intensive care unit-acquired (0.79 [0.64-0.97], p = .0272) groups.'] Are outcomes in severe sepsis and patients with septic shock : pathogen species and infection sites associated with mortality?