To evaluate the ability of clinicians to accurately dose antiepileptic drugs (AEDs), 2,958 serum concentrations in two outpatient epilepsy clinics were studied. Serum concentrations of phenytoin (PHT) were significantly less likely to fall within the therapeutic range (TR) when compared to carbamazepine (CBZ) or phenobarbital (p< 0.0001) even when there was evidence that patient compliance was good. This difference remained significant when the second through fourth follow-up serum concentrations were analyzed. PHT concentrations were more likely to be below than above the TR (p< 0.0001). CBZ concentrations were least likely of the three AEDs to be below the TR (p< 0.01). Analysis of factors influencing AED metabolism and of data from previous studies implies that saturable metabolism and variable time to steady state for PHT are responsible for these findings. These results support the increased use of dosing aids for PHT that may help clinicians more accurately choose PHT doses and estimate time to steady state.