OBJECTIVES: Ventilator-associated lower respiratory tract infections (VALRTIs) are among the most common ICU-acquired infections in patients receiving invasive mechanical ventilation (IMV). Immunocompromised patients may have a lower incidence of VALRTI when compared with nonimmunocompromised patients, but the influence of the type of immunosuppression on the epidemiology of VALRTI has not been investigated. The study objectives were to assess the association of the type of immunosuppression with the incidence, microbiology, and outcomes (ICU mortality, ICU length of stay, and duration of IMV) of VALRTI related to bacterial pathogens. DESIGN: Multicenter, international retrospective cohort study. SETTING: One hundred eighteen ICUs (118) in nine countries. PATIENTS: Eight hundred fifty-four immunocompromised adult patients (median age, 65 yr; 57.6% males) requiring IMV for greater than 48 hours, including 162 with hematologic malignancies. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with hematologic malignancies had a lower 28-day cumulative incidence of bacterial VALRTI than patients with other types of immunosuppression (13.6% vs. 20.1%; adjusted cause-specific hazard ratio, 0.61; 95% CI, 0.37–0.97), mostly due to a lower incidence of ventilator-associated pneumonia (9.3% vs. 13.9%). The proportion of VALRTI cases related to multidrug-resistant bacteria was similar between groups. Occurrence of bacterial VALRTI was associated with an increased mortality and a longer ICU length of stay, but this effect was independent of the type of immunosuppression. CONCLUSIONS: Patients with hematologic malignancies had a lower 28-day cumulative incidence of bacterial VALRTI than patients with other types of immunosuppression, mainly due to a lower incidence of ventilator-associated pneumonia.