ObjectiveTo explore the efficacy and safety of off-label use of domestically produced tenecteplase (TNK) for intravenous thrombolysis in the treatment of acute ischemic stroke (AIS) in the real world.MethodsA retrospective analysis was conducted on 350 AIS patients who received intravenous thrombolysis with domestically produced TNK or recombinant tissue plasminogen activator (rt-PA) within 4.5 hours of symptom onset at the First People's Hospital of Zhaoqing from April 2017 to January 2024. Patients were divided into the TNK group with 44 cases and the rt-PA group with 306 cases based on the medication. Baseline clinical data of patients were collected and compared, and the inverse probability weighting method based on propensity score (IPTW) method was employed to balance the differences of baseline clinical data between the TNK group and the rt-PA group. Symptomatic intracerebral hemorrhage (sICH) and early neurological deterioration (END) were used to evaluate the safety of intravenous thrombolysis. Patients were followed up for 3 months after thrombolysis, and the modified Rankin Scale (mRS) was employed to assess treatment efficacy. Differences in good prognosis, mRS scores, END, and sICH were compared between the TNK and rt-PA groups. Multivariate logistic regression analysis was performed to validate the robustness of the findings.ResultsAfter IPTW adjustment, no statistically significant differences were observed in baseline data (e.g., age, sex) between the two groups (all P > 0.05). The door-to-needle time (DNT) was significantly shorter in the TNK group than in the rt-PA group (Z=-2.602, P < 0.01). Comparisons of good prognosis, mRS scores, END, and sICH between the two groups showed no statistically significant differences (χ²/Z=0.949, -0.343, 0.395, 4.899; all P > 0.05). Multivariate Logistic regression analysis revealed no significant differences in the risks of good prognosis, END, or sICH between the TNK and rt-PA groups (OR=1.154, 0.729, 6.089; all P > 0.05).ConclusionFor AIS within 4.5 hours of onset, domestically produced TNK demonstrates comparable efficacy, safety, and cost-effectiveness to rt-PA for intravenous thrombolysis, suggesting TNK as a viable alternative treatment option.