BACKGROUND Although secondary infections are recognized as a cause of morbidity and mortality in seasonal influenza, their frequency, characteristics, and associated clinical outcomes in 2009 influenza A(H1N1) (A[H1N1])-related critical illness are unknown. METHODS In a prospective cohort of adult patients admitted to Canadian ICUs with influenza A(H1N1) infection, the frequency and associated clinical outcomes of prevalent (culture taken within 72 h of ICU admission) and ICU-acquired (culture taken after 72 h from ICU admission) positive bacterial cultures were determined. RESULTS Among 681 patients, the mean age was 47.9 years (SD, 15.1), APACHE (Acute Physiology and Chronic Health Examination) II score was 21.0 (9.9), and 573 patients (84.0%) were invasively mechanically ventilated. Positive cultures were obtained in 259 patients (38.0%): 77 (29.7%) had prevalent, 115 (44.4%) had ICU-acquired, and 40 (15.4%) had both; culture date was unavailable in 27 (10.4%). The most common bacterial organisms isolated were coagulase-negative staphylococci, Staphylococcus aureus, Pseudomonas species, and Streptococcus pneumoniae. Antibiotics were prescribed in 661 (97.1%), with 3.8 (1.9) prescriptions per patient. Patients with any positive culture had longer days of mechanical ventilation (mean [SD], 15.2 [10.7] vs 10.7 [9.0]; P<.0001), ICU stay (median [interquartile range (IQR)], 18.2 [12.5] days vs 10.8 [9.0] days, P<.0001), and hospitalization (median [IQR], 30.7 [20.7] days vs 19.2 [17.4] days, P<.0001) and a trend toward increased hospital mortality (25.1% vs 19.9%, P=.15). Patients with ICU-acquired positive cultures had worse outcomes compared with those with positive prevalent cultures or who were culture-negative. CONCLUSION Culture-based evidence of secondary infections commonly complicates A(H1N1)-related critical illness and is associated with worse clinical outcomes despite nearly ubiquitous antibiotic administration.