Residual renal function (RRF) in end-stage renal disease is clinically important as it contributes to adequacy of dialysis, quality of life, and mortality. This study was conducted to determine the predictors of RRF loss in a national random sample of patients initiating hemodialysis and peritoneal dialysis. The study controlled for baseline variables and included major predictors. The end point was loss of RRF, defined as a urine volume <200 ml/24 h at approximately 1 yr of follow-up. The adjusted odds ratios (AOR) and P values associated with each of the demographic, clinical, laboratory, and treatment parameters were estimated using an "adjusted" univariate analysis. Significant variables (P < 0.05) were included in a multivariate logistic regression model. Predictors of RRF loss were female gender (AOR = 1.45; P < 0.001), non-white race (AOR = 1.57; P = <0.001), prior history of diabetes (AOR = 1.82; P = 0.006), prior history of congestive heart failure (AOR = 1.32; P = 0.03), and time to follow-up (AOR = 1.06 per month; P = 0.03). Patients treated with peritoneal dialysis had a 65% lower risk of RRF loss than those on hemodialysis (AOR = 0.35; P < 0.001). Higher serum calcium (AOR = 0.81 per mg/dl; P = 0.05), use of an angiotensin-converting enzyme inhibitor (AOR = 0.68; P < 0.001). and use of a calcium channel blocker (AOR = 0.77; P = 0.01) were independently associated with decreased risk of RRF loss. The observations of demographic groups at risk and potentially modifiable factors and therapies have generated testable hypotheses regarding therapies that may preserve RRF among end-stage renal disease patients.