ObjectiveTo compare the efficacy and safety of perampanel (PER) and oxcarbazepine (OXC) monotherapy in the treatment of newly diagnosed focal epilepsy in adults. Methods A total of 62 adult patients with focal epilepsy, aged 18~79 years old, with an average age of (40.53±16.69) years, were enrolled from Qingyuan People’s Hospital between August 2021 and October 2022 and randomly divided into PER group and OXC groups. Both groups were followed up for 12 months and assessed for seizure free rate, effective rate, drug retention rate, and adverse reactions at 3, 6, and 12th months. ResultsThe results showed that the seizure free rate, effective rate, and drug retention rate in the PER group were 62.5%, 71.9% and 87.5% at 3 months, respectively, and 53.1%, 65.6% and 75.0% at 6 months respectively. In the OXC group, the seizure free rate, effective rate, and drug retention rate were 70.0%, 86.7%, and 93.3% at 3 months, respectively, and 66.7%, 73.3% and 83.3% at 6 months, respectively. At 12 months, the seizure free rate, effective rate and retention rate of the PER group were 43.8%, 46.9%, and 53.1%, respectively; The seizure free rate, effective rate, and retention rate of OXC group were 66.7%, 66.7%, and 70.0%, respectively. The incidence of adverse reactions in the PER group and OXC group was 15.6% and 16.7%, respectively. The most common adverse reactions in both groups were dizziness and drowsiness, with no serious adverse events. ConclusionPER and OXC monotherapy demonstrated similar efficacy and safety in the treatment of newly diagnosed adult focal epilepsy, and both drugs can be used as safe and effective treatment options.