ObjectiveThis study assesses the safety and efficacy of tirofiban for patients with large vessel occlusion stroke after intravenous thrombolysis. MethodsThis study data was from SUSTAIN, DEVT, and RESCUE BT trials. According to whether the use of tirofiban who underwent endovascular treatment and preceding intravenous thrombolysis was divided into the tirofiban group and the no-tirofiban group. The safety outcomes were symptomatic intracranial hemorrhage, any intracranial hemorrhage within 48 h, and 3-month mortality. The efficacy outcome was defined as a score of 0–2 on the modified Rankin Scale scores at 3 months. ResultsA total of 372 patients with intravenous thrombolysis were included in these SUSTAIN, DEVT, and RESCUE BT trials. Adjusted multivariate analysis showed that tirofiban with intravenous thrombolysis was not associated with symptomatic intracranial hemorrhage (aOR, 0.87; 95 % CI, 0.49–1.57; P=0.65), any intracranial hemorrhage within 48 h (aOR, 1.00; 95 % CI, 0.60–1.66; P=1.00), 3-month mortality (aOR, 1.10; 95 % CI, 0.56–2.19; P=0.78) and 3-month modified Rankin Scale scores 0–2 (aOR, 0.72; 95 % CI, 0.42–1.25; P=0.25) in patients with acute large vessel occlusion. In the subgroup analysis, we found that tirofiban was not recommended for females (aOR, 0.34; 95 % CI, 0.12–0.93), baseline Alberta Stroke Program Early CT Score≤9 (aOR, 0.37; 95 % CI, 0.18–0.76), and cardiogenic embolism (aOR, 0.36; 95 % CI, 0.14–0.97). ConclusionTirofiban combined with intravenous thrombolysis in patients with acute large vessel occlusion may be safe. Further studies need to confirm the effectiveness of tirofiban after intravenous thrombolysis in different stroke etiology.