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The aim of this study was to evaluate the clinical usage of second-line intravenous antiseizure medications (IV ASMs), particularly levetiracetam (LEV) and lacosamide (LCM), in patients with status epilepticus (SE) in relation to their clinical characteristics and the use of pre-existing ASM. In addition, we examined the ASM responses in relation to one another, an aspect that has rarely been investigated previously. This retrospective observational study was conducted at Tampere University Hospital. Data on SE patients aged ≥ 16 years who received IV ASM for the treatment of SE were retrieved from electronic patient register over a one-year period. Patient demographics, epilepsy history, pre-existing ASM therapy, and administered IV ASMs were recorded and SE episodes were classified by SE subtype. Second-line IV ASMs included LEV, LCM, valproate (VPA), and fosphenytoin (FPHT). A total of 78 SE episodes were identified in 72 patients (median age 68 years, 39% female). Among these, 40 were convulsive SE (CSE), 21 nonconvulsive SE (NCSE), 9 comatose NCSE, and 8 focal aware SE (FASE) episodes. The most used IV ASMs were LCM (47 episodes) and LEV (45 episodes), whereas VPA (7 episodes) and FPHT (2 episodes) were used infrequently. Patients under 68 years had higher response rates than older patients (68% vs. 43%, p = 0.046). Those treated with LEV were significantly older than those treated with LCM (median age 73 vs. 63 years, p = 0.002). Additionally, a prior epilepsy diagnosis was more frequent among patients receiving LCM as the first second-line IV ASM (63% vs. 28%, p = 0.005). Treatment was initiated with pre-existing ASM in 39% of cases. Notably, LCM as first second-line IV ASM demonstrated trend towards higher response rates than LEV (67% vs. 44%, p = 0.057). Following multivariable adjustment for age, sex, SE subtype, etiology, and time from seizure onset to ASM administration, LCM was associated with higher response odds compared to LEV (OR 3.29, 95% CI 1.06–10.19, p = 0.039), with no covariates demonstrating significant independent effects. The selection of ASM varied according to patients’ clinical characteristics. Patients treated with LCM tended to be younger and were more likely to have a prior diagnosis of epilepsy than those treated with LEV. LCM was associated with higher response rates than LEV, supporting its use as a viable alternative for the treatment of SE.