The clinical epidemiology of septicemia in dialysis populations remains poorly defined. In this historical cohort study of 393,451 U.S. dialysis patients, International Classification of Disease, Ninth Revision, Clinical Modification discharge diagnosis codes were used to compare first-year septicemia admission rates in annual incident cohorts from 1991 to 1999 and to calculate subsequent cardiovascular event and mortality rates. Hemodialysis (compared with peritoneal dialysis) as initial therapy and starting dialysis in more recent years were the principal antecedents of septicemia. In hemodialysis patients, adjusted first admission rates (expressed throughout as first episodes per 100 patient-years) rose by 51%, from 11.6 in 1991 to 17.5 in 1999. In peritoneal dialysis patients, rates rose from 5.7 in 1991, peaked at 9.2 in 1997, and declined to 8.0 in 1999. Mortality rates after septicemia were similar to mortality rates after major cardiovascular events. Septicemia was associated with developing myocardial infarction, congestive heart failure, stroke, and peripheral vascular disease with adjusted risk ratios of 4.1, 5.5, 4.1, and 3.8 in the initial 6 mo after admission for septicemia and 1.7, 2.0, 2.0, and 1.6 after 5 yr, respectively. Septicemia, which is associated with increased cardiovascular and death risk, has become more common in dialysis patients in the United States.