The Early Randomized Surgical Epilepsy Trial (ERSET) aimed to determine whether early surgical therapy for drug-resistant temporal lobe epilepsy (TLE) is superior to continued medical management in controlling seizures and improving quality of life (QOL). The trial was conducted at 16 US epilepsy surgery centers and included 38 participants with mesial temporal lobe epilepsy (MTLE) who had disabling seizures for no more than 2 consecutive years after adequate trials of two antiepileptic drugs (AEDs). Participants were randomized to either continued AED treatment or anteromesial temporal resection (AMTR) plus AED treatment. The primary outcome was freedom from disabling seizures during the second year of follow-up. Secondary outcomes included QOL, cognitive function, and social adaptation. The results showed that zero of 23 participants in the medical group and 11 of 15 in the surgical group were seizure-free during the second year (odds ratio=∞; 95% CI, 11.8 to ∞; P<.001). In an intention-to-treat analysis, the surgical group showed a higher improvement in QOLIE-89 overall T-score compared to the medical group, but this difference was not statistically significant. When data from the medical group participants who underwent surgery were excluded, the effect of surgery on QOL was significant (12.8 vs 2.8 points; treatment effect=9.9; 95% CI, 2.2 to 17.7; P=.01). Memory decline occurred in 36% of participants after surgery, consistent with literature rates. Adverse events included a transient neurological deficit attributed to a postoperative stroke and three cases of status epilepticus in the medical group. The study concluded that early surgical therapy plus AED treatment resulted in a lower probability of seizures during the second year of follow-up compared to continued AED treatment alone, but the trial was prematurely terminated due to slow accrual.The Early Randomized Surgical Epilepsy Trial (ERSET) aimed to determine whether early surgical therapy for drug-resistant temporal lobe epilepsy (TLE) is superior to continued medical management in controlling seizures and improving quality of life (QOL). The trial was conducted at 16 US epilepsy surgery centers and included 38 participants with mesial temporal lobe epilepsy (MTLE) who had disabling seizures for no more than 2 consecutive years after adequate trials of two antiepileptic drugs (AEDs). Participants were randomized to either continued AED treatment or anteromesial temporal resection (AMTR) plus AED treatment. The primary outcome was freedom from disabling seizures during the second year of follow-up. Secondary outcomes included QOL, cognitive function, and social adaptation. The results showed that zero of 23 participants in the medical group and 11 of 15 in the surgical group were seizure-free during the second year (odds ratio=∞; 95% CI, 11.8 to ∞; P<.001). In an intention-to-treat analysis, the surgical group showed a higher improvement in QOLIE-89 overall T-score compared to the medical group, but this difference was not statistically significant. When data from the medical group participants who underwent surgery were excluded, the effect of surgery on QOL was significant (12.8 vs 2.8 points; treatment effect=9.9; 95% CI, 2.2 to 17.7; P=.01). Memory decline occurred in 36% of participants after surgery, consistent with literature rates. Adverse events included a transient neurological deficit attributed to a postoperative stroke and three cases of status epilepticus in the medical group. The study concluded that early surgical therapy plus AED treatment resulted in a lower probability of seizures during the second year of follow-up compared to continued AED treatment alone, but the trial was prematurely terminated due to slow accrual.