OBJECTIVESThere are limited data available demonstrating the safety and efficacy of intravenous tenecteplase versus alteplase in patients with acute ischemic stroke in the posterior circulation.MATERIALS AND METHODSThis is a post-hoc analysis of the Alteplase compared to Tenecteplase (AcT) pragmatic, phase 3, registry-linked randomized controlled trial. Patients with any posterior circulation vessel occlusion on baseline imaging were included. Study outcomes included 90-day modified Rankin Scale (mRS) 0-1, mRS 0-2, ordinal mRS, death within 90 days, 24 h symptomatic intracerebral haemorrhage (sICH) and successful reperfusion/recanalization. Mixed effects regression adjusting for age, sex and stroke severity was used to analyze differences in outcomes between patients administered tenecteplase vs. alteplase. Further, sensitivity analysis was conducted for basilar artery occlusion (BAO) alone.RESULTSOf 1577 patients, 136 (8.6 %, 77:alteplase, 59:tenecteplase) had posterior circulation stroke. Baseline characteristics were similar[median age 71 (IQR 60-81) vs. 72 (IQR 65-82) years, 57.1 % vs. 67.8 % males, median baseline NIHSS 7 (IQR 4-12) vs. 7 (IQR 4-16) in alteplase vs. tenecteplase arms, respectively]. 28 patients (20.6 %, 16:alteplase, 12:tenecteplase arm) underwent EVT. The median 90-120 days mRS was 2 (IQR 1-4). There were no differences between alteplase and tenecteplase for 90-d mRS 0-1 (adjRR 0.93;95 %CI 0.63-1.36), 90-day mRS 0-2 (adjRR 0.95; 95 %CI 0.72-1.26), sICH (RR 0.65; 95 %CI 0.06-7.02) and mortality (RR 1.21; 95 %CI 0.61-2.38). Successful reperfusion eTICI 2b-3 and successful recanalization rAOL 2b-3 was achieved in 23/28 (82 %, 12:alteplase, 11:tenecteplase) and in 16/28 (57 %, 14:alteplase, 12:tenecteplase), respectively. Similar results were seen in 31 patients (22.8 %) with BAO.CONCLUSIONIntravenous tenecteplase has a similar effect on outcome as alteplase, without increased safety concerns in patients with acute posterior circulation strokes.