Purpose Levetiracetam (LEV) therapeutic range (20-40 mg/L) and potential drug interactions were assessed in people with epilepsy (PWE). Method Fifty-two PWE had LEV and concomitant medications [carbamazepine (CBZ); valproate (VPA); lamotrigine (LTG)] blood levels measured and compared to seizure activity. Lacosamide (LCM) levels were unavailable. Adopted therapeutic ranges were: 20-40 mg/L - LEV; 25-50 孯l/L - total CBZ; 6-13 孯l/L - free CBZ; 300-750 孯l/L - total VPA; 30-75 孯l/L - free VPA; and 40-60 孯l/L - LTG. Seizure-freedom was assessed and patients followed for almost two years. Results 23 of 52 PWE (44%) used LEV monotherapy and 16/23 (70%) had 'therapeutic' LEV with 13/16 (81%) seizure-free. 29 of 52 (56%) used polytherapy and 16/29 (55%) had 'therapeutic' LEV with 7/16 (44%) seizure-free. 11 of 29 (38%) used CBZ: 4/11 (36%) had therapeutic mean LEV levels and 7/11 (64%) were seizure-free. Fourteen (48%) used VPA: 9/14 (64%) had therapeutic mean LEV levels and 8/14 (57%) were seizure-free. 13 of 29 (45%) used LTG: 8/13 (62%) had therapeutic mean LEV levels and 5/13 (38%) were seizure-free. LEV did not alter CBZ, but CBZ affected LEV. LEV elevated VPA free levels but not VPA total levels. Dosage/concentration was lowered with polytherapy. Conclusion LEV range (20-40 mg/L) assisted epilepsy management and anti-epileptic medication interactions were suggested with polytherapy thus possibly explaining the impaired efficacy of LEV with polytherapy.