Whether preceding transient ischemic attack (TIA) can provide neuroprotective benefits in subsequent acute ischemic stroke (AIS) caused by large vessel occlusion remains unclarified. This study aimed to investigate the association between preceding TIA and functional outcomes in AIS patients with endovascular therapy (EVT). Eligible patients were divided into TIA and non-TIA groups according to whether they experienced TIA within 96 hours prior to stroke. Two groups were balanced using propensity score matching (PSM) analysis at a 1:3 ratio. Onset stroke severity and 3-month functional independence were evaluated. A total of 887 patients were included. After PSM, 73 patients with and 217 patients without preceding TIA were well matched. Onset stroke severity was not different between the groups (p > 0.05). However, the TIA group had a lower systemic immune-inflammation index (SII) (median, 1091 versus 1358, p < 0.05). Preceding TIA was significantly associated with 3-month functional independence (adjusted odds ratio, 2.852; 95% confidence interval [CI], 1.481-5.495; adjusted p < 0.01). The effects of preceding TIA on functional independence were partially mediated by SII (average causal mediation effects 0.02; 95% CI, 0.001-0.06, p < 0.05). In AIS patients treated by EVT, preceding TIA within 96 hours was associated with three-month functional independence but not with reduced onset stroke severity.