<i>Background:</i> A part of ischemic stroke patients score 0 on the National Institutes of Health Stroke Scale (NIHSS) within 24 h following thrombolysis. Their clinical characteristics and long-term outcome are poorly studied. We report a single-center assessment of such patients. <i>Methods:</i> The cohort comprises 874 consecutive patients from the Helsinki Stroke Thrombolysis Registry, out of whom 113 scored 0 on 24-hour NIHSS. We analyzed their baseline demographic, clinical and radiological characteristics and 3-month outcome (modified Rankin Scale, mRS). Associations between the study parameters were tested by multivariate analysis. <i>Results:</i> Patients with a 24-hour NIHSS score = 0 (n = 113) were younger than the rest of the population (n = 761; median: 65.6 vs. 71.5 years; p < 0.001), their NIHSS score on admission was lower (median: 5 vs. 10; p < 0.001), as was their glucose level (median: 6.2 vs. 6.7 mmol/l; p = 0.02). The onset-to-treatment time was similar in both groups (median: 120 vs. 115 min; p = 0.89). Patients with a 24-hour NIHSS score = 0 more often achieved an excellent outcome (mRS scores: 0–1; 81 vs. 31%; p < 0.001) and had lower mortality (1.8 vs. 11.8%; p < 0.01). One third of these patients had a brain infarction visible on 24-hour imaging. Lower baseline NIHSS score and younger age were independently associated with 24-hour NIHSS score = 0, which, in turn, was independently associated with excellent 3-month outcome. <i>Conclusions:</i> Patients with an NIHSS score = 0 at 24 h following thrombolysis are younger, have milder symptoms and have a lower glucose level on admission. They achieve more often excellent outcome and lower mortality. Still, 8% of them required help in daily activities or were dead at 3 months (mRS scores: 3–6).