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Objective To compare the relationship of plasma iohexol clearance to standard adequacy measures in an automated peritoneal dialysis (APD) population. Design Prospective, nonrandomized, open label, simultaneous clearance studies of novel (iohexol) and traditional (urea and creatinine) markers of dialysis quantitation. Setting Outpatient peritoneal dialysis units associated with tertiary care university hospitals. Patients Eighteen stable patients, 13 undergoing continuous cycling peritoneal dialysis (CCPD) and 5 receiving intermittent dialysis, who underwent 24-hour clearance studies were enrolled in and completed the study. Interventions Each subject received 15 mL of iohexol intravenously the morning of a scheduled dialysis night. Blood was obtained for determination of serum concentrations of urea nitrogen and creatinine, and plasma iohexol concentration. Dialysate and urine were collected over 24 hours. Main Outcome Measures Urea and creatinine data from the total pooled dialysate and from the 24-hour urine collection were used to calculate daily Kt/V urea and normalized total daily creatinine clearance (CrCI). Total plasma iohexol clearance was calculated using a one-compartment model with the Bröchner-Mortensen correction. Results Normalized [to 1.73 m2 body surface area (BSA)] iohexol clearance correlated very well with normalized CrCI (r2 = 0.777; p < 0.001). A weaker correlation was observed between Kt/V urea and normalized iohexol clearance (r2 = 0.213; 0.05 < p < 0.1). When data are not normalized using BSA or urea distribution volume, the regressions are improved for both creatinine (r2 = 0.820) and urea (r2 = 0.533). These results were comparable between those on CCPD and those on intermittent therapy. Conclusion Total plasma iohexol clearance provides a simple assessment for APD adequacy by eliminating collection problems inherent to the methodologies currently employed. Such simplicity allows for more frequent assessments of delivered dialysis dose and efficacy of prescription changes.