The aim of the present study was to determinate the factors affecting carbamazepine (CBZ) clearance (CL) in adults with epilepsy using a mixed-effect model and sparse data collected during routine clinical care. The patient population comprised 104 adults receiving CBZ. A total of 161 CBZ steady state serum concentration samples were analyzed. Population CL was calculated by using NONMEM with a one compartment model with first-order absorption and elimination. The following covariates were tested for their influence on clearance (CL): total body weight, age, dose/day, sex, surface area (SA) and comedication with primidone (PRIM), ualproic acid or phenytoin (DFH). The final regression model for carbamazepine clearance found best to describe the data was: CL = (0.614 SA + 0.0016 dose/day)(1 + 0.278 DFH)(1 + 0.326 PRIM).