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The perioperative mortality of total knee and hip arthroplasties (TKA, THA) remains a major concern among health care providers and their patients. The increase in utilization of TKA and THA makes it imperative to be aware of factors that are associated with this unfortunate event. Therefore we analyzed the Nationwide Inpatient Sample data from 1998 to 2008 and compared admissions with perioperative mortality to those that survived their hospitalization. An estimated total of 4,438,213 TKA and 2,182,121 THA procedures were performed in the United States between 1998 and 2008. The average mortality rate for TKA was 0.13% and 0.18% for THA, or 0.34 and 0.44 events per 1,000 inpatient days, respectively. Independent risk factors for in-hospital mortality were advanced age, male gender, ethnic minority background, emergency admission as well as a number of comorbidities and complications. Furthermore, we demonstrated that the timing of death occurred earlier after TKA when compared to THA, with 50% of fatalities occurring by day 4 versus day 6 of the hospitalization, respectively. This study provides nationally representative information on risk factors for and timing of perioperative mortality after TKA and THA. Our data can be used to assess the risk for perioperative mortality and to develop targeted intervention to decrease such risk. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1811-1821, 2012 [ABSTRACT FROM AUTHOR]