Patients with juvenile myoclonic epilepsy (JME) may have uncontrolled seizures. The purpose of this study was to investigate the use and challenges with antiepileptic drugs (AEDs) and the patients' view of these challenges. A questionnaire about the use of AEDs, adherence to therapy, and quality of life was given to patients with JME recruited from Drammen Hospital. Data regarding AEDs were confirmed from medical records at Drammen Hospital, Norway (2007–2018). Additional clinical interviews were performed, and a mixed method approach was applied. Ninety patients with defined JME diagnosis, 54/36 women/men aged 14–39 (mean: 25) years, were included. Only 29 (33%) were seizure-free. Within the last year, 21% experienced generalized tonic–clonic seizures (GTCS), and 68% had myoclonic jerks. Seventy-six (84%) used AEDs, 78% in monotherapy. A total of 10 AEDs were used;: most commonly valproate (n = 33), lamotrigine (n = 27), and levetiracetam (n = 21). Two-thirds of valproate users were men while all other AEDs were used more in females than in men. Valproate and levetiracetam displayed better efficacy against GTCS than lamotrigine. One-third often/sometimes forgot their medication nonintentionally while 14% had intentional poor adherence. The majority reported good quality of life (76%). No significant correlations between the use of AEDs, use of valproate, poor adherence, quality of life score, and seizure freedom were demonstrated. Half of the patients had serum concentrations measured every year, and two-thirds thought this was important. Qualitative interviews elucidated treatment challenges in JME;, adverse effect burden, adherence, and activities of daily life. Despite the use of AEDs in the majority of patients, only one-third were seizure-free. Other challenges included polypharmacy, the use of valproate in women, and variable adherence. This points to a need for closer follow-up in patients with JME. Unlabelled Image • Despite use of AEDs in the majority of 90 patients with JME, only one third were seizure free • Valproate, lamotrigine and levetiracetam were the most commonly used AEDs • Gender differences with more men using valproate and more women using lamotrigine and levetiracetam were demonstrated • Valproate and levetiracetam displayed better efficacy against GTCSs than lamotrigine • Challenges in these patients include persisting seizures, polypharmacy with risks of interactions, adverse effects, use of valproate in women, and variable adherence [ABSTRACT FROM AUTHOR]