Background: The therapeutic value of second-generation anticonvulsants such as lamotrigine has not been clearly established in neonates and infants with seizures. To address this issue, we assessed the efficacy of lamotrigine for treating neonatal and infantile seizures, detailed the dosing regimens used, and described its tolerability and safety profile. Methods: This retrospective study included patients (age 0-12 months) diagnosed with seizures and treated with lamotrigine, as monotherapy or adjunctive therapy, by pediatric neurologists at Centre mère-enfant Soleil du CHUQ from 2004 to 2014. The frequency of seizures and EEG patterns were compared before and after introduction of lamotrigine during the first months of life. Data on initial and maintenance doses, rate and magnitude of dosing increments, and adverse effects were collected. Results: Treatment with lamotrigine was initiated in 32 neonates and 13 infants. At first follow-up (mean duration 3 months), 76 % (n = 34) showed a significant (≥50%) reduction of seizures and 64% (n= 29) improvement of EEG pattern compared to baseline. The efficacy in monotherapy and adjunctive therapy was similar. A single case of cutaneous hypersensitivity reaction requiring cessation of treatment was reported. Conclusions: This study suggests that lamotrigine is a useful, safe, and well-tolerated anticonvulsant alternative for the treatment of seizures in neonates and infants.