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Background Intravenous thrombolysis (IVT) is guideline-recommended prior to endovascular thrombectomy (EVT), yet its benefit for anterior circulation large vessel occlusion (LVO) patients requiring interhospital transfer remains uncertain. IVT may facilitate early recanalization (ER) and obviate EVT, but may also delay treatment and necessitate acute blood pressure (BP) lowering—both of which can accelerate infarct progression. We assessed whether collateral status modifies the efficacy and safety of bridging thrombolysis (BT) in transfer patients.Methods We conducted a single-center retrospective study of anterior circulation LVO patients undergoing interhospital transfer for EVT. Patients receiving IVT were compared to those who did not, with utility-weighted modified Rankin Scale (uwmRS) as the primary outcome. Collateral status was graded on CT angiography arterial phase using the Tan score. Inverse probability of treatment weighting (IPTW) balanced cohorts on prespecified baseline covariates; doubly robust analyses further adjusted for residual imbalances (SMD >0.10) and LASSO-selected variables. Multivariable models examined associations of IVT and collateral status with ER and infarct progression (ASPECTS decay during transfer). Interaction and causal mediation analyses evaluated whether collateral status modifies IVT’s effectiveness and safety.Results Among 359 patients, 193 (53.8%) received IVT. Overall, IVT was not associated with improved uwmRS (adjusted β −0.006 [95%CI −0.068 to 0.057], p=0.86), though a significant interaction indicated benefit with better collaterals and potential harm with poorer collaterals (interaction p=0.016, figure 1). IVT was associated with higher odds of ER (OR 13.53 [95%CI 4.66-39.27], p<0.001), but also longer time-to-EVT (+54.6 min [95%CI 21.1-88.1], p=0.002) and greater infarct progression before EVT (β +0.71 [95%CI 0.33-1.09], p<0.001). Better collateral status independently predicted higher ER rates (OR 1.72 [95%CI 1.14-2.60], p=0.010) and less infarct progression (β −0.86 [95%CI −1.13 to −0.59], p<0.001). Causal mediation analysis demonstrated that IVT-facilitated ER translated to superior uwmRS only in good-collateral patients (TAN 2-3, Average Causal Mediation Effect [ACME] 0.02 [95%CI 0.003 to 0.05], p=0.022). In contrast, infarct progression culminated in significant IVT-associated harm only among poor-collateral patients (TAN 0-1, ACME -0.05 [95%CI -0.12 to -0.01], p=0.012).Conclusions BT was not associated with net clinical benefit overall, likely due to concurrently elevated odds of ER and greater infarct progression. Collateral status significantly modulated this balance, where good collaterals amplify the benefit of IVT-facilitated ER, and poor collaterals amplify the potential harms of treatment delays and infarct progression. Collateral assessment may help guide patient-level BT decisions.Disclosures L. Franco Castro: None. M.K. McIntyre: None. S. Rewinkel: None. H. Chen: None. A. Malhotra: None. D. Lakhani: None. M. Colasurdo: None.Abstract E-274 Figure 1