Invasive disease due to Acinetobacter baumannii is an increasing problem in health care settings worldwide. Whether certain clones of A. baumannii are more likely to cause invasive disease in hospitalized patients is unknown. We studied all patients at a public teaching hospital in Houston, Texas, from whom the Acinetobacter calcoaceticus-Acinetobacter baumannii complex was isolated over a 14-month period in 2005 to 2006. One hundred seven unique patient isolates were identified, with 87 of the strains classified as being A. baumannii, the majority of which were multidrug resistant. The A. baumannii isolates were comprised of 18 unique pulsed-field types, with strains of clone A and clone B accounting for 66 of the 87 isolates. Epidemiologic analysis showed the predominance of the two A. baumannii clones at distinct time periods, with the remainder of the A. baumannii and non-A. baumannii strains being evenly distributed. Patients from whom clone A strains were isolated were more likely to be bacteremic than were patients with other A. baumannii isolates. Conversely, clone B strains were more likely to be isolated from patients with tertiary peritonitis. Patients from whom clone A was isolated had a significantly higher rate of mortality. Multilocus sequence typing demonstrated that clones A and B are related to each other and to A. baumannii strains previously isolated in Western Europe, sharing five of seven alleles. Taken together, we conclude that the outbreak of the A. calcoaceticus-A. baumannii complex in our institution was due to two distinct A. baumannii clones that were associated with significantly different patient outcomes.