Care of patients with end-stage renal disease (ESRD) is important and resource intense. To enable ESRD programs to develop strategies for more cost-efficient care, an accurate estimate of the cost of caring for patients with ESRD is needed. The objective of our study is to develop an updated and accurate itemized description of costs and resources required to treat patients with ESRD on dialysis therapy and contrast differences in resources required for various dialysis modalities. One hundred sixty-six patients who had been on dialysis therapy for longer than 6 months and agreed to enrollment were followed up prospectively for 1 year. Detailed information on baseline patient characteristics, including comorbidity, was collected. Costs considered included those related to outpatient dialysis care, inpatient care, outpatient nondialysis care, and physician claims. We also estimated separately the cost of maintaining the dialysis access. Overall annual cost of care for in-center, satellite, and home/self-care hemodialysis and peritoneal dialysis were US $51,252 (95% confidence interval [CI], 47,680 to 54,824), $42,057 (95% CI, 39,523 to 44,592), $29,961 (95% CI, 21,252 to 38,670), and $26,959 (95% CI, 23,500 to 30,416), respectively (P < 0.001). After adjustment for the effect of other important predictors of cost, such as comorbidity, these differences persisted. Among patients treated with hemodialysis, the cost of vascular access-related care was lower by more than fivefold for patients who began the study period with a functioning native arteriovenous fistula compared with those treated with a permanent catheter or synthetic graft (P < 0.001). To maximize the efficiency with which care is provided to patients with ESRD, dialysis programs should encourage the use of home/self-care hemodialysis and peritoneal dialysis. Copyright 2002 by the National Kidney Foundation, Inc.