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Background Stroke rates rise steeply with age but data on tenecteplase in patients ≥80 years remain limited. This post-hoc analysis of the AcT trial compared tenecteplase with alteplase in this population.Methods The analysis included all Alteplase Compared to Tenecteplase in Patients with Acute Ischemic Stroke (AcT) trial participants aged 80 years or older who were randomised to tenecteplase (0.25 mg/kg single bolus) or alteplase (0.9 mg/kg over 60 min). The primary outcome was excellent functional recovery (Modified Rankin Scale (mRS) score: 0–1 at 90–120 days). Secondary outcomes included mRS score 0–2, ordinal mRS shift and safety endpoints including symptomatic intracerebral haemorrhage (sICH) and mortality. Generalised mixed-effects models adjusted for baseline covariates with site as a random effect. Exploratory analyses examined the treatment-by-time interaction using continuous onset-to-needle time (OTN), outcomes by endovascular thrombectomy (EVT) status and outcomes in patients aged≥90 years.Results Among 543 patients aged ≥80 years (286 tenecteplase, 257 alteplase; mean age 86.9 years), baseline characteristics were balanced. Rates for mRS 0–1 (22.7% vs 23.1%; adjusted RR 0.94, 95% CI 0.74 to 1.19; p=0.63) and mRS 0–2 (37.4% vs 35.5%; adjusted RR 1.02, 95% CI 0.85 to 1.13) were similar, with no significant shift across the ordinal mRS distribution. Mortality (24.5% vs 27.3%) and sICH (3.5% both groups) did not differ. Longer OTN was associated with lower functional independence (adjusted OR per 30 min delay 0.89, 95% CI 0.77 to 1.03), although this did not reach statistical significance. Outcomes were consistent across EVT (n=149) and non-EVT (n=394) subgroups and in patients aged ≥90 years (n=160).Conclusions Tenecteplase and alteplase showed comparable efficacy and safety in patients ≥80 years supporting tenecteplase as a reasonable alternative to alteplase in elderly stroke patients.