Vancomycin pharmacokinetic data in critically ill patients receiving sustained low-efficiency dialysis (SLED) is limited. Published data using vancomycin with intermittent hemodialysis and continuous renal replacement therapy may not be applicable to hybrid dialysis modalities such as SLED. Current drug references lack recommendations for vancomycin dosing in patients receiving SLED. The objective of this study was to determine vancomycin pharmacokinetics during SLED. A total of 20 patients who were critically ill with oliguric or anuric renal failure who received vancomycin and SLED were included in the study. Surrounding one SLED session, serum vancomycin blood samples were drawn before the initiation of SLED, at the termination of SLED, and 4 hours after completion of SLED treatment. Following this, patients received vancomycin, dosed to target a goal peak of 20-30 mcg/ml. A vancomycin peak level was drawn 1 hour after the end of the infusion. SLED treatment duration was at least 7 hours. Continuous data are reported as median (interquartile range) and categorical data as percentage. The vancomycin elimination rate and half-life were 0.051 hours (0.042-0.074 hours) and 13.6 hours (9.4-16.6 hours), respectively. SLED reduced vancomycin serum concentrations by 35.4% (31.5-43.8%), and vancomycin rebound was 9.8% (2.5-13.7%). The vancomycin dose administered post-SLED was 1000 mg (875-1125 mg). For 18 patients, the patient-specific volume of distribution was 0.88 L/kg (0.67-1.1 L/kg), vancomycin clearance was 3.5 L/hr (2.2-5.2 L/hr), and the area under the concentration-time curve during the study time period was 280.8 mg·hr/L (254.7-297.3 mg·hr/L). Vancomycin is significantly removed during SLED with little rebound in serum concentrations 4 hours after completion of SLED. Based on study findings, patients who are critically ill require additional vancomycin dosing after each SLED session to maintain therapeutic post-SLED vancomycin concentrations. Therapeutic drug monitoring of vancomycin is recommended during SLED. © 2020 Pharmacotherapy Publications, Inc.