Purpose The purpose of this study was to determine whether seizure recurrence has a negative impact on cognition, psychological function, and health-related quality of life (HRQoL) over a 12-month period of monotherapy in adults with newly diagnosed or previously untreated partial epilepsy. Methods Seizure freedom (SF) was defined as no seizure recurrence during the 40-week maintenance period of medication. Neuropsychological tests, the Symptom Checklist—90 (SCL-90), and the Quality of Life in Epilepsy—31 (QOLIE-31) were administered at baseline and after 48weeks of carbamazepine or lamotrigine monotherapy. Seventy-three patients successfully continued treatment until the 48-week follow-up time point. Fifty patients (68.5%) had SF, and the remaining 23 were not seizure-free (NSF). A seizure outcome group-by-time interaction was analyzed using a linear mixed model. Results A group-by-time interaction was identified for the total QOLIE-31 score (p<0.05) and score on two QOLIE-31 subscales (social function: p<0.001 and seizure worry: p<0.001), with a significant improvement over time only present in the SF group (all p<0.001). There was no significant group-by-time interaction for most cognitive function tests, with the exception of the serial clustering score (p<0.01) and number of recognition hits on the California Verbal Learning Test (p<0.05). Serial clustering did not differ between the SF and NSF groups at baseline, but was significantly more used in the NSF group than in the SF group at 48weeks (p<0.01). There was no significant group-by-time interaction for any dimension of the SCL-90. Conclusion Recurrent seizures had a significant effect on HRQoL, a subtle effect on cognitive performance, and no effect on psychological symptoms over one year in newly diagnosed or previously untreated adults with partial epilepsy.