INTRODUCTION: Thrombolysis (IVT) is effective in the treatment of lacunar stroke (LAC). However, most studies compared the outcome of LAC to a heterogenous control group. We aimed to compare early neurological improvement (ENI) and late functional outcomes following thrombolysis for LAC with a homogenous control group of cardioembolic stroke (CE) without large-vessel occlusion (LVO). PATIENTS AND METHODS: Patient data were obtained from the national multicentre STAY ALIVE Acute Stroke Registry. At each centre, a team of vascular neurologists determined the TOAST classification. ENI was defined as a minimum 4-point decrease in the NIHSS score between admission and discharge, or a complete resolution of symptoms. For late functional outcome, we analysed the dichotomised 90-day mRS scores (good outcome was mRS≤2). RESULTS: 142 LAC and 156 CE patients were analysed. Following IVT, the percentage of ENI did not differ significantly (LAC 41.1% vs CE 49.7%, p=0.154), and multivariable analysis did not identify any clinical parameters that would predict ENI after IVT in either group. LAC patients had unfavourable, albeit non-significant, odds of having good 90-day functional outcomes compared to CE patients (aOR 0.483, 95% CI 0.201-1.161, p=104). CONCLUSIONS: We report the first analysis of short- and long-term outcomes of IVT in LAC, using a homogenous control group of CE patients without LVO. The prevalence of ENI and 90-day functional outcomes were similar. However, LAC patients had unfavourable odds of achieving good functional outcomes compared to the control group. Therefore, we emphasise that LAC should not be considered a minor stroke subtype.