Purpose <p>Lacosamide (LCS) is a third-generation antiseizure medication (ASM) approved for focal-onset seizures and generalized epilepsy. Although the branded formulation, Vimpat^®, has shown efficacy and safety, the introduction of generic versions, such as Stutan^®, raises concerns about clinical equivalence, especially considering the potential for therapeutic fluctuations that could result in breakthrough seizures or adverse events. This study aimed to compare the real-world efficacy, safety and tolerability of branded lacosamide (Vimpat^®) versus its generic counterpart (Stutan^®) in patients with focal or generalized epilepsy.</p> Methods <p>A multicenter, retrospective, observational study was conducted at two epilepsy centers in Southern Italy. Sixty adult patients were included and divided into two groups: Group A (<i>n</i> = 30) received branded LCS and Group B (<i>n</i> = 30) received the generic formulation. Data were collected at treatment initiation (T0) and the first follow-up (T1), including seizure frequency, adverse events and dose adjustments. The primary outcome was the responder rate (≥ 50% reduction in seizure frequency), with secondary outcomes including seizure freedom, adverse events and dose changes.</p> Results <p>Baseline characteristics were similar between groups. The average daily LCS dose was significantly higher in the Vimpat^® group (275 ± 121&#xa0;mg) compared to the Stutan^® group (168 ± 89&#xa0;mg, <i>p</i> &lt; 0.001). Despite this, efficacy outcomes were comparable, with 60.0% of patients in Group A and 43.3% in Group B achieving a ≥ 50% seizure reduction (<i>p</i> = 0.08). Adverse events were mild or moderate.</p> Conclusions <p>In this real-world setting, generic LCS (Stutan^®) demonstrated comparable efficacy, safety and tolerability to Vimpat^®, supporting its clinical use as a valid alternative in epilepsy management.</p>