Objective: This study was designed as an open-label trial to assess the effects of changing the antiepileptic drugs (AEDs) regi-men to lamotrigine (LTG) as adjunctive/monotherapy in patients with partial seizures who were dissatisfied with their drug regimen because of intractable seizures. Methods: The patients were recruited from multicenters using the following criteria: age≥18 years; at least 3 seizures per month during the last 16 weeks; previous use of at least 3 AEDs. The study involved a baseline phase and 2 experimental phases: LTG was first added to the regimen, and then patients could gradually change to LTG monotherapy if their seizures were reduced by at least 50 percent/month. Tolerability, the primary end point, was assessed using the Liverpool Adverse Experience Profile (LAEP). Secondary end points included quality of life, as measured with the Quality of Life in Epilepsy-31 inven-tory. Reductions in seizures from baseline throughout each phase were also analyzed. Results: One hundred and fourteen patients aged between 18 and 52 years (age 27.8±13.2 years; 71 men and 43 women) were enrolled. After adding LTG, 105 patients (92.11%) completed adjunctive therapy. Upon completion of the adjunctive phase, mean improvement from baseline was 2.6 points on the LAEP (p=0.037). The overall score on the QOLIE-31 improved by 8.49 points from baseline (p=0.023). At the end of the trial, 26 (22.81%) of patients completed LTG monotherapy, and 65 patients (57.02%) experienced at least 50% reduction in seizure frequency compared to baseline, The mean improvement from baseline was 5.1 points on the LAEP (p=0.0059), and the overall score on the QOLIE-31 score improved by 12.72 points from baseline(p=0.0071). Twenty-two (19.30%) patients reported adverse effects and 9 patients discontinued participation in the trial because of adverse effects. Conclusion: For patients with partial seizures who were dissatisfied with their AED regimen because of intractable seizures, adding LTG to the drug regimen was well tolerated and effective in improving the quality of life and controlling seizures. Furthermore, switching to LTG monotherapy was associated with further improvement.