This open-label, 6-year continuation study of several short-term clinical trials was conducted to assess the long-term tolerability and efficacy of lamotrigine when used as adjunctive therapy or monotherapy for partial seizures in adult patients (⩾16 years) with epilepsy. Study visits occurred every 24 weeks throughout the treatment period. Of the 527 patients enrolled in the long-term continuation study, 508 were exposed to lamotrigine for at least 6 months (including their exposure in the primary clinical study), and 248 were exposed to lamotrigine for at least 5 years. Of the 527 patients, 75 received initial lamotrigine exposure during this study. Investigators judged that overall clinical status at the end of the study or at time of discontinuation (whichever occurred first) was improved moderately or markedly relative to prelamotrigine clinical status for 36% of patients. The most common treatment-emergent adverse events (regardless of suspected cause) were dizziness, diplopia, and headache. The only serious treatment-emergent adverse event occurring at a frequency exceeding 2% was accidental injury (2.7% of patients). Adverse events prompted 28 patients to discontinue from the study. The most common adverse events leading to discontinuation were dizziness (1.3%), headache (0.8%), rash (0.8%), and somnolence (0.6%). All adverse events resolved without sequelae. Lamotrigine administered as monotherapy or adjunctive therapy during a 6-year open-label continuation study was associated with a low incidence of adverse events in adult patients with epilepsy.