In April 2009, CDC reported the first two cases in the United States of human infection with a novel influenza A (H1N1) virus. As of July 6, a total of 122 countries had reported 94,512 cases of novel influenza A (H1N1) virus infection, 429 of which were fatal; in the United States, a total of 33,902 cases were reported, 170 of which were fatal. Cases of novel influenza A (H1N1) virus infection have included rapidly progressive lower respiratory tract disease resulting in respiratory failure, development of acute respiratory distress syndrome (ARDS), and prolonged intensive care unit (ICU) admission. Since April 26, communitywide transmission of novel influenza A (H1N1) virus has occurred in Michigan, with 655 probable and confirmed cases reported as of June 18 (Michigan Department of Community Health [MDCH], unpublished data, 2009). This report summarizes the clinical characteristics of a series of 10 patients with novel influenza A (H1N1) virus infection and ARDS at a tertiary-care ICU in Michigan. Of the 10 patients, nine were obese (body mass index [BMI] >or=30), including seven who were extremely obese (BMI =40); five had pulmonary emboli; and nine had multiorgan dysfunction syndrome (MODS). Three patients died. Clinicians should be aware of the potential for severe complications of novel influenza A (H1N1) virus infection, particularly in extremely obese patients.