Background and Objectives: Despite achieving ideal reperfusion (eTICI = 3) through endovascular treatment (EVT), some acute ischemic stroke (AIS) patients still experience poor outcomes. This study aims to evaluate the efficacy and safety of tirofiban in AIS patients with ideal reperfusion, focusing on its effects in large artery atherosclerosis (LAA) and cardioembolic (CE) stroke. Methods: A total of 474 AIS patients from the RESCUE-BT database were included. Patients were assigned to either the tirofiban or placebo group based on the treatment received. The primary outcome was favorable functional recovery at 90 days (mRS <= 2), and safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day mortality. Multivariable logistic regression was used to adjust for confounders, and subgroup and interaction analyses assessed tirofiban's efficacy in LAA and CE populations. Results: In the overall population that achieved ideal reperfusion, Tirofiban did not improve clinical outcomes and did not increase the risk of mortality or incidence of sICH (p > 0.05). However, subgroup analysis indicated potential clinical benefits for patients with higher NIHSS scores in the LAA group, especially in the subgroup with NIHSS scores >13 (adjusted OR 4.671, 95% CI [1.545, 14.122]). No significant differences were found in the CE group. Conclusions: Tirofiban showed potential benefits for LAA patients with ideal reperfusion, especially those with NIHSS scores above 13. Careful patient selection is recommended.