Background: Body weight and body mass index (BMI) are regularly assessed factors in stroke patients for manifold reasons. However, their potential role specifically in intravenous thrombolysis has not been thoroughly examined. Methods: Data from 865 consecutive acute ischemic stroke patients treated with intravenous thrombolysis were analyzed. Patients were divided into different BMI categories (underweight, normal weight, overweight, obese) and compared based on the following factors: time window of treatment, clinical scores National Institute of Health Stroke Scale Score (NIHSS), modified Rankin scale (mRS) on admission and discharge, risk factors, stroke characteristics and thrombolysis complications. Recombinant tissue plasminogen activator (rtPA) doses relative to body weight and blood volume were also assessed. In a separate analysis, patients weighing up to 100 and >100 kg were compared. Results: Eighteen patients (2.1%) were underweight, 336 (38.8%) overweight, 194 (22.4%) obese and 317 (36.7%) had normal weight. Higher BMI category was associated with younger age, thrombolytic treatment later than 4.5 h, arterial hypertension, diabetes and higher relative rtPA dose relative to blood volume (p < 0.001). There were no significant differences concerning NIHSS and mRS scores or thrombolysis complications. Forty-six patients (5.3%) weighed over 100 kg. They were younger (p = 0.002) and treated later than patients under 100 kg (p < 0.001). Mean rtPA dose relative to body weight and to blood volume was significantly lower (0.7 vs. 0.9 mg/kg, p < 0.001 and 13 vs. 13.9 mg/l, p < 0.001). There was a marginal difference in NIHSS score improvement ≥4 points (26.1 vs. 40.2%, p = 0.038); otherwise, no outcome differences were found. Conclusion: BMI category does not significantly influence clinical outcome after thrombolysis. However, relevant NIHSS improvement was found more often in patients weighing up to 100 kg compared to those over 100 kg. Interestingly, patients with higher BMI or weight >100 kg were thrombolysed later than other patients.