To describe the characteristics and determinants of outcome of hospital-acquired bloodstream infection (HA-BSI) due to respiratory infection among patients admitted to intensive care units (ICUs). We performed a post hoc analysis of the EUROBACT multicenter cohort study, conducted in 162 ICUs in 24 countries. The HA-BSIs due to candidemia and from mixed respiratory and nonrespiratory sources were excluded. From the overall 1156 included in EUROBACT, 230 patients were classified as having HA-BSI respiratory infections (HA-BSI requiring ICU admission, n=40; ICU-acquired noninvasively ventilated respiratory BSI, n=30; and ICU-acquired invasively ventilated BSI, n=160) and were compared with 749 patients with HA-BSI not related to respiratory infections. HA-BSI respiratory infections were more frequently due to gram negatives (76.3% vs. 56.7%, P<0.0001), mainly Acinetobacter baumannii (18.3% vs. 10.4%, P=0.0007), Klebsiella spp. (18.7% vs. 11%, P=0.0013), and were less frequently because of gram-positive cocci (23.3% vs. 41.2%, P<0.0001), with the exception of Staphylococcus aureus (11.3% vs. 9.5%, P=0.39). HA-BSI respiratory infections were more frequently associated with multiple drug-resistant pathogens (53.9% vs. 42.7%, P=0.0003), were more common in medical patients, and were more likely to be ICU-acquired as compared with nonrespiratory infections. After adjustment for severity and other risk factors, HA-BSI of respiratory origin was a risk factor for day-28 mortality (odds ratio=1.52 [1.02-2.27], P=0.04). Among the cohort of 230 patients with HA-BSI of respiratory origin, those with HA-BSI requiring ICU admission presented more often with septic shock (24/40=60%) as compared with ICU-acquired HA-BSI episodes occurring in noninvasively (9/30=30%) and invasively (71/160=44%, P=0.04) ventilated patients. Recovered microorganisms were similar between the 3 groups of HA-BSI of respiratory origin. When adjusted for confounding factors, the risk of death was lower for ICU-acquired HA-BSI occurring among invasive ventilated patients (odds ratio=0.41 [0.19-0.92], P=0.03) than for patients not invasively ventilated before HA-BSI of respiratory origin. The EUROBACT multicenter study confirms that the lung as a respiratory source of infection is associated with more gram-negative resistant pathogen and a poorer prognosis. When associated with BSI, lung infections occurring in noninvasively mechanical ventilated patients are associated with more septic shock and a worse prognosis than patients with bacteremic ventilator-associated pneumonia.