Abstract Body: Background: Acute ischemic stroke can result from extracranial arterial dissection. The effectiveness and safety of intravenous thrombolysis (IVT) for acute ischemic stroke in these cases, particularly those involving large vessel occlusions, are debated. We conducted a systematic review and metanalysis to assess the efficacy and safety of IVT in patients with acute ischemic stroke attributed to extracranial arterial dissection. Methods: This systematic review was registered in PROSPERO (CRD42024499774). We searched MEDLINE (OVID), EMBASE, web of Science, and SCOPUS from inception to 03/03/2024. Search terms included a combination of keywords and controlled vocabulary terms for carotid or vertebral artery dissection and fibrinolysis or alteplase or tenecteplase. We included randomized controlled trials, observational studies, case series that compared IV thrombolysis and standard management with at least 10 patients in each group in patients with cervical or vertebral artery dissection. Where studies were sufficiently similar, we performed metanalyses for benefits (excellent (0-1) and good (0-2) modified Rankin scale at 90 days), safety (symptomatic intracerebral hemorrhage (sICH)), and mortality outcomes, using relative risks (RR). Given the impact of NIHSS on 90-day modified Rankin Scale, we pooled adjusted ORs (adjusting for NIHSS) when exploring 90-day functional outcomes. Results: Our search identified 418 records, we screened 12 studies as potentially eligible. Four studies (all retrospective cohort, 3 studies adjusted for NIHSS variable, one study addressed LVO cohort) met our inclusion criteria. The risk of bias was assessed using the Risk of Bias in Nonrandomized Studies of Interventions tool. Two studies had serious risk of bias while the other two had a moderate bias risk. When compared no IVT, IVT was associated with comparable risk of sICH (RR, 0.91 [95% CI, 0.11-7.94]) and mortality (RR, 0.63 [95% CI, 0.29-1.37]). However, IVT was associated with a significantly higher odds of good functional outcome at 90-days (aOR, 1.53 [95% CI, 1.14-2.05]) and a non-significantly lower chance of excellent functional outcome at 90-days (aOR 2.16 [95% CI 0.72-6.51]). Conclusion: Our metanalysis suggests that in patients with acute ischemic stroke secondary to extracranial artery dissection, IVT may have improved efficacy but comparable safety and mortality. Our findings should be interpreted with caution until supported by randomized controlled trials.