Vigabatrin (VGB) has been shown to be particularly effective in the treatment of infantile spasms for those with tuberous sclerosis complex (TSC). However, many patients with TSC continue to have treatment-resistant seizures. For many patients with TSC, partial-onset seizures are prominent. Therefore, we examined the efficacy and tolerability of VGB for treatment of refractory partial-onset seizures. We performed a retrospective cohort study on 49 TSC patients with treatment-resistant seen at our center from 1997 to 2010, examined seizure outcomes, and reported adverse effects. We found that 13 (24.5%) patients became seizure-free or experienced a >90% decrease in seizure episode frequency with the addition of VGB to their regimens. Only one patient stopped VGB use because of excess sedation. The remaining 21 patients discontinued VGB use because of lack of efficacy. We conclude that VGB may be a safe and effective treatment in TSC patients with refractory partial-onset seizures.