OBJECTIVE To identify the most advantageous formula for estimating creatinine clearance (CCr) and to establish a dose of dialysis that will ensure minimal acceptable levels of creatinine clearance in patients on continuous peritoneal dialysis (CPD). METHODS Analysis of all CCr studies performed in CPD patients over 40 months. METHODS All four dialysis units following CPD patients in one city. One dialysis unit is government-owned, one is university-affiliated, and two are community based. METHODS One hundred and ninety-four patients representing almost the entire CPD population in Albuquerque. METHODS Creatinine and urea clearance studies were performed in 24-hour urine and drained dialysate samples. Creatinine clearance (peritoneal plus urinary) was normalized to either 1.73 m2 body surface area (CCr) or body water estimated by the Watson formulas (KT/VCr). CCr and KT/VCr were either corrected by averaging urinary creatinine and urea clearances or were not corrected. Two dialysis units were designated as the training set (92 patients, 143 clearance studies) and the other two units as the validation set (102 patients, 181 clearance studies). METHODS Minimal acceptable creatinine clearance levels were determined in the training set by computing the creatinine clearance value corresponding to 1.70 weekly KT/V urea by linear regression. Logistic regression models predicting low creatinine clearance were developed in the training set and were tested in the validation set. RESULTS The following weekly creatinine clearance values corresponded to 1.70 KT/V urea: corrected CCr 52.0 L/1.73 m2, uncorrected CCr 54.4 L/1.73 m2, corrected KT/VCr 1.46, uncorrected KT/VCr 1.53. Logistic regression identified as predictors of low creatinine clearance low daily urine volume (UV) and low daily dialysate drain volume/body water (DV/V) for all four creatinine clearance formulas, plus low/low-average peritoneal solute transport (only for uncorrected CCr) and serum creatinine (for both KT/VCr formulas). In the validation set, the predictive models produced an area under the receiver operating characteristic (ROC) curve between 0.835 and 0.919 indicating very good predictive accuracy. For corrected CCr and anuria, the regression model produced a minimal normalized drain volume (DV/V) value consistent with minimal acceptable CCr equal to 0.305 L/L per 24 hours. This DV/V cutoff detected low corrected CCR in validation set anuric subjects (n = 55) with a sensitivity of 85% and a specificity of 71%. For uncorrected CCR and anuria, DV/V cutoffs were 0.273 L/L per 24 hours (high/high-average peritoneal solute transport) and 0.420 L/L per 24 hours (low/low-average transport). Sensitivity and specificity of these cutoffs in validation set anuric subjects were 87% and 85%, plus 86% and 33%, respectively. CONCLUSIONS The uncorrected CCr appears to be the most advantageous creatinine clearance formula in CPD, because it allows the use of peritoneal solute transport type in the calculation of the minimal required normalized drain volume. The minimal acceptable uncorrected CCr is 54.4 L/1.73 m2 weekly. To achieve this uncorrected CCr in anuria, the required minimal normalized drain volume is 0.273 L per liter of body water daily if peritoneal solute transport is high or high-average and around 0.420 L per liter of body water daily if peritoneal solute transport is low or low-average. The required total daily drain volume is computed by multiplying the required normalized drain volume by body water.